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Starch (Carbohydrate) Digestion and AbsorptionMetabolic support for nutrient absorption -
When you are stressed, the brain releases stress hormones such as cortisol that makes your heart beat faster. This causes the body to devote its energy to deal with stress.
As a result, the digestive process slows down which in turn affects the process of nutrient absorption. Being stressed also slows down the gastric emptying and intestinal transit time and affects the digestion, absorption, and metabolism of nutrients present in food.
Moreover, it is also advised to eat mindfully by savouring eat and every bite. As it not only helps you to chew properly and break down the food into easily assimilated and digestible form but also enhances the nutrient absorption.
Make it a habit to avoid distractions such as using phones or watching TV while having meals. Also, relish every bite you eat as it helps in the secretion of the digestive juices in the stomach and allows it to mix with the ingested food.
We have always been told that eating a fruit is better than drinking the juice. However, it is not always true. It turns out that nutrient absorption from certain types of juices is better than the whole fruit. This is because the fibre present in whole fruit may bind to certain micronutrients which keeps these nutrients from getting absorbed in the small intestine.
However, the levels of vitamin C absorbed from whole oranges and orange juice remain the same. Drinking orange juice every time is not a good idea as it lacks fibre. Hence, it is advised to eat the fruit as well as drink orange juice to get the most of the nutrients from the fruit.
According to the Journal of Food Science, you can even try a smoothie which retains the fibre from fruits and vegetables along with improving the absorption of various nutrients. However, as a general rule, it is advised to chew your fruits properly than drinking juices.
Include probiotics and prebiotics in diet. Most of us are aware of the fact that probiotics are good for the gut health. Probiotics as well as fermented foods which contain microorganisms are not only good for digestion but also help in the absorption of nutrients[4].
The bacteria help in breaking down the food particles, thereby maximizing the absorption of nutrients by the intestine.
Hence, include probiotics such as yoghurt and fermented foods like kimchi, buttermilk, pickles etc in your diet to up the nutrient absorption. Foods like legumes, potatoes and oats, which are prebiotic foods, can also help to absorb nutrients from food.
These are non-digestible food components which act as food for the gut biome. Moreover, dietary fibre is known to enhance the absorption of minerals such as magnesium, iron, and calcium. Bottom line: There are numerous factors that can impact your digestive process and prevent absorption of nutrients from your food.
This is the reason why making these simple tweaks in your diet can help you to make the most of the nutrients available through food and stay healthy. The article is reviewed by Dr. Lalit Kanodia, General Physician. Cassady BA, Hollis JH, Fulford AD, Considine RV, Mattes RD.
Mastication of almonds: effects of lipid bioaccessibility, appetite, and hormone response. Am J Clin Nutr. Kiecolt-Glaser JK. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Psychosom Med. Aschoff JK, Kaufmann S, Kalkan O, Neidhart S, Carle R, Schweiggert RM. In vitro bioaccessibility of carotenoids, flavonoids, and vitamin C from differently processed oranges and orange juices [Citrus sinensis L. J Agric Food Chem. Heller KJ. Lastly, we highlight how the gut microbiota impact small intestinal nutrient-sensing in normal physiology, and in disease, pharmacological and surgical settings.
Emerging evidence indicates that the molecular mechanisms of small intestinal nutrient sensing in metabolic homeostasis have physiological and pathological impact as well as therapeutic potential in obesity and diabetes.
An increase in high-calorie intake and a sedentary lifestyle have resulted in continually increased rates of obesity, with ~2 billion adults affected by overweight or obesity 1. These dire statistics, along with their associated health care costs, underscore the critical need for safe and effective therapeutic interventions.
However, in spite of significant advances in furthering our understanding of the pathophysiology of metabolic disease, costly and invasive bariatric surgery remains the best current treatment for obesity and diabetes 3 , 4.
Besides bariatric surgery, many pharmacological agents available for treating people with diabetes and obesity work by manipulating the gut-derived hormone glucagon-like peptide-1 GLP-1 , altogether highlighting the importance of the gastrointestinal GI tract in developing interventions for diabetes and obesity.
The GI tract was once thought to be primarily a site for nutrient absorption. It is now, however, well-established that the GI tract detects nutrients and triggers integrative and biological responses involving endocrine and neural components. The GI tract represents the first site of interaction between a meal and the host, informing the central nervous system CNS about the size and composition of a meal.
The gut also contains the enteric nervous system that responds to a meal by adjusting GI physiology to maximize and optimize digestion and absorption 5.
These GI nutrient-sensing mechanisms, together with the effects of the postprandial rise in glucose, lipids, and amino acids, are vital for energy and glucose homeostasis via direct and indirect neural and endocrine mechanisms at various organs.
While the glucose-sensing pathways in other tissues, such as the pancreas, liver, and brain also impact metabolic regulation, they have been reviewed elsewhere 6 , 7 , 8. This review will focus on the preabsorptive role that intestinal nutrients have on metabolic homeostasis through nutrient-sensing mechanisms, with an emphasis on the regulation of food intake and systemic glucose regulation.
Furthermore, we will highlight how obesity and diabetic settings alter these pathways, and how host—microbe crosstalk via diet-induced changes in the small intestinal microbiome impacts these pathways. The GI tract consists of the small and large intestine, which differ in anatomy and function.
The primary site of nutrient absorption takes place on the apical side of the polarized epithelial cell layer of the upper small intestine, while nutrients activate metabolic and sensory signaling pathways in the mucosal layer to exert whole-body biological responses before being absorbed into the circulation.
Stem cells within the GI tract differentiate into multiple cell types, including secretory cells such as a hormone-producing and -secreting subtype enteroendocrine cells EECs 9 Fig. EECs are scattered throughout the intestinal epithelium and are the key cell type that senses nutrients and initiates subsequent signaling by secretion of gut hormones.
The classical rigid definition of EECs was based on the hormone they secrete in response to nutrient sensing, such as L-cells or I-cells secreting GLP-1 and cholecystokinin CCK , respectively. However, EECs in reality exhibit a large degree of heterogeneity in hormone expression and secretion, as well as spatial expression along the GI tract as evident in single-cell RNA-Seq experiments 9 , 10 , Importantly, these studies examined small intestinal EECs 9 , 10 , 11 , highlighting the fact that a large population of EECs i.
Comparatively, there are high levels of EECs in the large intestine, but their activation may not be due to direct nutrient exposure, but rather from a neurohumoral reflex 12 or other stimuli Glucose, lipids, and protein from ingested foods are taken up by small intestinal enterocytes for cellular metabolism and absorption.
Preabsorptive nutrients also activate enteroendocrine cells, triggering the release of GLP-1 and CCK. CCK and GLP-1 enter the circulation and act directly on peripheral organs to regulate metabolism. In parallel, CCK and GLP-1 act on the vagus nerve innervating the small intestine or portal vein as well as interact with the enteric nervous system to regulate glucose and energy homeostasis.
Ingested nutrients trigger feedback mechanisms to prevent postprandial energy excess by suppressing food intake and endogenous nutrient production Fig.
In addition to GLP-1 and CCK, EECs secrete up to 20 varieties of gut peptides that decrease energy intake and regulate glucose homeostasis. However, we will herein focus mostly on GLP-1 and CCK, the most studied small intestinal gut peptides that target the vagal afferents, brain, and pancreas to regulate energy and glucose homeostasis.
Although the post-prandial feedback mechanisms are partly coordinated by direct interaction of the liver, pancreas, and brain with circulating nutrients 6 , 7 , 8 , nutrient-induced small intestinal signaling mechanisms drive a majority of this feedback.
This is attributed to the glucoregulatory effect of GLP-1 and another gut peptide glucose-dependent insulinotropic polypeptide GIP , in which the peptides are released from the small intestine in response to glucose sensing Recently, the role of the upper small intestinal GLP-1 secreting cells is highlighted by selectively knocking out Gcg expression a gene from which GLP-1 is derived in the lower gut ileum and large intestine In response to oral glucose challenge, distal Gcg knockout mice responded with normal levels of secreted plasma active GLP-1, thereby unveiling the importance of upper small intestinal GLP-1 secreting cells in glucose-sensing Small intestinal-derived peptides act in an endocrine fashion on the peripheral and CNS targets or in a paracrine fashion on vagal afferent neurons.
These neurons are in close proximity to the gut, contain receptors for GLP-1, CCK, and peptide YY PYY and terminate in the nucleus of the solitary tract of the hindbrain where it has been demonstrated to regulate energy and glucose homeostasis Alternatively, gut peptides may activate the enteric nervous system to relay information to the vagal afferent terminals via glutamate or nitric oxide 18 , 19 , although the difficulty in targeting enteric neurons per se in vivo has limited the understanding of the role of the enteric nervous system in mediating the effects of nutrient-sensing.
Nevertheless, the role of gut—brain vagal signaling pathways in metabolic homeostasis is demonstrated by the fact that chemical, surgical, genetic, or viral manipulation of the vagal gut—brain pathway impairs nutrient-induced regulation of energy and glucose homeostasis.
This is reviewed in detail elsewhere GLP-1R is expressed in the vagal afferent neurons, pancreas, and the brain Knockdown of the GLP-1R in vagal afferent neurons via lentiviral injection into the nodose ganglia the inferior ganglion of the vagus nerve , which enables knockdown throughout the vagus nerve, increases meal size and postprandial glycemia, and blunts insulin release 22 while knocking down GLP-1R via the use of transgenic mice in the gut—brain neuronal axis leads to increased glucose levels In addition to the gut—brain metabolic axis governed by the glucose sensing in the small intestine, glucose sensing in the portal vein can be triggered by intestinal gluconeogenesis induced by protein and fiber intake and activate a portal vagal—brain axis to regulate glucose and energy homeostasis Overall, nutrient-sensing in the small intestine plays a major role in gut—brain negative feedback signaling that regulates energy and glucose homeostasis Fig.
Small intestinal lipid sensing suppresses food intake through the release of CCK and GLP-1 and the activation of vagal afferents. It is traditionally believed that lipid sensing in the small intestine occurs on the apical luminal side where long-chain fatty acids LCFA are absorbed and metabolized to generate sensory anorectic signals.
The Intralipid effect is blocked by the local anesthetic tetracaine, which inhibits nerve impulses, indicating small intestinal vagal innervation as a mediator of the anorectic signals Further, co-infusion of lipid with a lipase inhibitor blocks the ability of lipid to suppress food intake, as well as increase CCK and GLP-1 Inhibition of chylomicron formation with Pluronic L attenuates the anorectic effect, celiac and cervical vagal afferent activation, and gut peptide release induced by lipids 33 , Similarly, infusion of fatty acids with a chain length of less than C10 which do not assemble in chylomicrons but directly diffuse out of enterocytes fails to reduce energy intake and increase CCK levels in humans These observations argue against the traditional view of lipid sensing that occurs on the apical luminal side of the small intestine, prior to absorption.
Indeed, despite studies that elucidated the role of the receptor GPR40 and GPR to a lesser extent in mediating LCFAs to stimulate gut peptides release 36 , the cellular site of action apical vs. basolateral has not been fully elucidated.
Recently, utilizing an isolated intestinal perfusion model, it was shown that linoleic acid and GPR40 agonists induce GLP-1 release only when infused into the vasculature that would target the basolateral side, and not to the apical lumen In cultured, stable, immortalized murine EECs GLP-1 secretion is dependent on lipoprotein lipase to hydrolyze chylomicrons and on GPR40 to bind the liberated LCFAs 38 , further supporting that activation of EECs by LCFAs occurs on the basolateral side through hydrolysis of newly synthesized chylomicrons.
Additionally, CD36 a protein that transports fatty acids into cells and is documented to mediate chylomicron formation 39 knockout mice have impaired CCK release and fail to suppress food intake in response to duodenal lipids 40 , 41 , indicating that chylomicron formation in the small intestine is necessary for lipid sensing to lower food intake and thereby supporting the basolateral sensing hypothesis Fig.
a Mechanisms of small intestinal lipid sensing. The hydrolysis of chylomicrons by nearby enterocytes on the basolateral membrane may lead to increased LCFAs that can activate basolateral GPR40 to induce peptide release.
b Mechanisms of small intestinal carbohydrate sensing. However, ileal glucose sensing may stimulate the release of GLP-1 independent of SGLT1.
In response to high-fat feeding or obesity, small intestinal SGLT1 expression is reduced, leading to an impairment of glucose sensing, GLP-1 secretion, and glucose control.
c Mechanisms of small intestinal protein sensing. Luminal small oligopeptides and amino acids are taken up by PepT1 and amino acid transporters, respectively, into the enterocyte and enteroendocrine cells. Small intestinal protein sensing stimulates the release of CCK and GLP-1 and regulates feeding and glucose homeostasis potentially via PepT1 dependent mechanisms.
In addition, amino acids stimulate peptide release via the membrane-bound calcium-sensing receptor, the umami taste receptor, and G-protein-coupled receptor 6A.
However, the downstream mechanism mediating the peptide release remains elusive. In parallel, amino acids are also transported to the basolateral side, and studies implicated that they may activate the calcium-sensing receptor to stimulate GLP-1 secretion.
Vagal afferent fibers mediate the anorectic effects of intestinal lipid-sensing and are activated by several gut peptides Vagal afferents contain CCK-1 receptor CCK-1R and selective knockdown of CCK-1R in vagal afferents abolishes the ability of CCK to lower food intake However, the impact of vagal CCK-1R on small intestinal lipid-induced CCK signaling has not been established Vagal afferents also express GLP-1R 42 , and at least one study reports that GLP-1 signaling mediates the suppressive effects of jejunal linoleic acid infusion However, GLP-1R-expressing vagal afferent neurons were also reported to detect stomach and intestinal stretch but have no impact on nutrient-sensing Thus, the effect of GLP-1R on intestinal lipid sensing remains unclear.
It is possible that the enteric nervous system, which contains GLP-1R, may mediate the gut—brain effect instead 18 , Utilizing pancreatic—euglycemic clamps with plasma insulin levels maintained at a basal non-stimulated condition, upper small intestinal lipid infusion lowers hepatic glucose production In contrast, a study with human participants reports that during the pancreatic—euglycemic clamps, no difference in glucose production is detected in response to intraduodenal infusion of lipid vs control group However, this observation is made in the presence of a progressive rise in plasma insulin and glucose levels prior to the start of the lipid or control infusion, and a parallel progressive drop in both plasma free fatty acids and glucose production in both groups Thus, it is not surprising that glucose production is not further lowered by intraduodenal lipid vs.
saline infusion in a state that mimics the postprandial state, in which hepatic glucose production is already inhibited. Similar to lipid-induced reductions in food intake, the ability of small intestinal lipid infusion to lower hepatic glucose production is dependent on CCK and GLP-1 signaling during the pancreatic basal insulin -euglycemic clamps 45 , Further, inhibiting CCK-1R signaling during refeeding, which activates nutrient-sensing pathways, results in postprandial hyperglycemia The specific mechanisms leading to the release of CCK and subsequent effects on glucose homeostasis are not fully understood, although the esterification of fatty acids to fatty acyl-CoA via acyl-CoA synthetase and the subsequent activation of mucosal protein kinase C PKC -δ are necessary for rats 46 , This is consistent with the fact that LCFA induces CCK release in intestinal secretin tumor cells via PKC-δ activation In parallel, the formation of chylomicron is also implicated in CCK release 50 , but the underlying mechanisms of how lipids stimulate CCK to release overall remain elusive Fig.
Further, the specific role of vagal GLP-1R signaling in mediating the glucoregulatory effect of lipids remains to be clarified. In addition to lowering hepatic glucose production via a gut—brain axis 45 , 46 , small intestinal lipid-sensing could regulate glucose homeostasis via GLPinduced increase in insulin or suppression of glucagon secretion, as lipid-sensing increases GLP-1 release 45 ,.
However, GLP-1 induced increase in insulin secretion requires the presence of elevated circulating glucose levels Thus, it is possible that while an infusion of lipid alone increases GLP-1, this would not substantially elevate plasma insulin levels in the absence of a concomitant rise in blood glucose levels, as reported in human studies 52 , Despite this, increasing circulating active GLP-1 levels during an Intralipid intestinal infusion via DPP-IV inhibition inhibits degradation of GLP-1 decreases glucose and increases insulin levels In addition, while GLP-1 is known to suppress glucagon secretion, glucagon is consistently increased with Intralipid infusion 52 , Although it has not been evaluated, this unexpected effect of Intralipid on glucagon could be due to the concurrent CCK release, as CCK lowers the inhibitory effect of glucose on glucagon secretion A high-fat diet HFD impairs lipid-induced gut—brain feedback regulating both energy and glucose homeostasis.
Intestinal sensing of lipids is impaired during HFD in both rodents and humans 55 , however, it is still contentious as to whether this is due to chronic exposure to HFD or induction of obesity. For example, studies in rats have shown that the combination of an HFD with a genetic background that is predisposed to obesity, is associated with reduced intestinal-lipid sensing 56 , Furthermore, HFD decreases postprandial active GLP-1 and CCK levels in obese-prone rats compared to obese-resistant rats, potentially due to decreased intestinal expression of GPR40 and GPR, receptors that are implicated in lipid-sensing induced secretion of gut peptides 56 , 57 , 58 Fig.
The importance of interaction between diet and obesity for nutrient-sensing is also supported by human data. A 2-week high-fat dietary regimen in humans does not impair the suppressive effects on appetite or the CCK and GLP-1 response to an intralipid duodenal infusion However, individuals with obesity are less responsive to the satiating effects of dietary fat 60 , Obesity is also associated with reduced postprandial gut peptide levels 62 , and specifically for lipid-sensing, CCK release is blunted in individuals affected by obesity following intraduodenal oleic acid Therefore, future studies need to delineate the effect of diet vs.
phenotype, which may be due to the ability of the gut microbiota to mediate this interaction between the diet and host physiology discussed in more detail below.
Besides reductions in lipid-induced gut peptide release, it is possible that diminished sensitivity to gut peptides contributes to the reduced responsiveness to intestinal fat sensing in feeding control.
The anorectic effect of CCK is impaired in HFD-fed mice and rats 55 , as is vagal afferent activation 55 , although this has not been fully examined in humans. Further, CCK-1R expression in vagal nerves is decreased in HFD induced obese rats 56 , ultimately contributing to reduced nodose ganglia cocaine and amphetamine-regulated transcript CART expression, a neuropeptide regulating energy homeostasis, in association with increased food intake and body weight However, vagal CCK resistance during obesity could also be due to obesity-associated leptin resistance, as the leptin receptor is co-expressed with CCK-1R in the vagal afferent neurons 65 and leptin potentiates the suppressive effect of CCK on appetite and increases vagal afferent activation following CCK administration 66 , Using both genetic and viral approaches, the knockdown of leptin receptors in vagal afferent neurons impairs CCK responsiveness and induces hyperphagia Taken together, it is possible that impairments in CCK signaling both at the level of secretion and vagal activation could drive reduced lipid-induced satiation, although much of this remains to be tested in humans.
HFD also impairs the ability of upper small intestinal lipid sensing to improve glucose tolerance and lower hepatic glucose production 45 , The loss of effect of lipid-sensing following short-term 3-day HF feeding is partly due to impaired vagal CCK-1R signaling as both Intralipid and CCK but not upstream activation of vagal protein kinase A fail to lower glucose production in HF rats 25 , 46 , In parallel, HFD lowers upper small intestinal long-chain acyl-CoA synthetase-3 expression and disrupts long-chain acyl-CoA synthetase-3 dependent small intestinal fatty acid metabolism to regulate glucose homeostasis.
However, transplantation of healthy microbiome to HF rats rescues the glucoregulatory effect of lipid-sensing via upregulation of long-chain acyl-CoA synthetase-3 expression in a small intestinal farnesoid x receptor FXR dependent fashion The underlying mechanism of how HF-induced changes in small intestinal microbiome alter bile acid pool, FXR, acyl-CoA synthetase-3, and lipid sensing remains elusive.
Nonetheless, we hypothesize that enhancing long-chain acyl-CoA synthetasedependent upper small intestinal fatty acid metabolism could increase GLP1 action to regulate glucose homeostasis in spite of CCK-1R vagal resistance Fig.
Intraduodenal infusion of glucose dose-dependently suppresses food intake in rodents 72 , and reduces food intake 73 , 74 or favorably influences subjective appetite ratings 73 in humans.
Intravenous infusion of glucose to match the levels observed in blood following intestinal infusion of glucose does not inhibit food intake in rodents and humans 72 , 75 , highlighting the role of preabsorptive intestinal glucose-sensing. GLP-1R antagonist Exendin-9 abolishes the anorectic effect of both intragastric and voluntary sucrose loads in rats 76 , indicating that GLP-1 action mediates the effect of carbohydrate-sensing on food intake.
Glucose-induced GLP-1 secretion from small intestinal EECs is dependent on sodium-glucose luminal transporter-1 SGLT-1 As non-metabolizable sugars transported via SGLT-1 also induce GLP-1 release 79 , glucose-sensing appears to be dependent on the transport of glucose via SGLT-1 but independent of subsequent cellular glucose metabolism.
This finding has been confirmed in the human small intestine However, recent studies report that non-caloric sweeteners do not induce GLP-1 release in primary L-cells and rodents 79 , 83 , and in humans, noncaloric sweeteners fail to induce gut peptide release and have no effect on appetite It is possible that the suppressive effect of glucose on food intake depends on the specific site of the small intestine where glucose is sensed.
For instance, a greater reduction of energy intake associates with higher CCK levels in humans receiving duodenal versus jejunal infusion of glucose However, in another study 86 , glucose infusion into the ileum, but not duodenum, suppresses food intake, and a rodent study similarly found that ileal glucose infusion suppresses food intake to a greater degree than duodenal glucose infusion These studies support the notion that ileal nutrient-sensing regulates gut motility 88 but later proposed by many to also regulate food intake In contrast to the upper small intestine, this may be due to SGLT-1 independent glucose-mediated GLP-1 release 90 Fig.
Small intestine infusion of glucose impacts glucose homeostasis and the effects are not only due to glucose absorption into circulation. First, it is well established that the GI tract contributes to insulin secretion via the incretin effects of GLP-1 and GIP, which stimulate insulin secretion from the pancreas.
Direct infusion of glucose into the duodenum in humans also increases circulating insulin levels, as does jejunal infusions, while glucagon levels either decrease or remain unchanged This discrepancy in glucagon is likely due to the differing actions of GIP and GLP-1, as GIP paradoxically increases while GLP-1 inhibits glucagon secretion While both GLP-1R and GIPR knockout mice exhibit reduced insulin release in response to intestinal glucose, each model only exhibits mild glucose intolerance.
However, dual GLP-1R and GIPR knockout mice exhibit substantially impaired glycemic control and oral glucose-stimulated insulin release as compared to single incretin receptor knockout mice Further, GIP was found to be a more powerful incretin hormone than GLP-1, but its overall effect on glucose homeostasis is likely masked by the concomitant rise in glucagon As such, the common hepatic branch of the vagus, as well as celiac and gastric branches, are all implicated in contributing to the glucoregulatory effects of GLP-1 action 94 , For example, selective knockdown of GLP-1R in the nodose ganglia impairs glucose response to a mixed meal but interestingly does not impair oral glucose tolerance This implies that the impaired response to a mixed meal challenge is not dependent on altered intestinal glucose-sensing.
Further, the impact of genetic knockout of GLP-1R in vagal neurons on oral glucose tolerance is contentious 22 , However, selective restoration of the islet and pancreatic duct GLP-1R in global GLP-1R knockout mice was sufficient to improve impaired oral glucose tolerance, although the reason for this is unknown as there was no change in glucose-stimulated insulin release among the groups Thus, the mechanism of glucose-induced GLP-1 regulation on insulin secretion remains elusive.
Direct infusion of glucose into the upper small intestine or jejunum given at a dose that does not increase portal glucose levels activates small intestinal SGLT-1 and lowers hepatic glucose production in parallel to an increase in portal GLP-1 levels 97 , 98 Fig.
Similar to the mechanism of glucose-sensing in the regulation of food intake, infusion of non-metabolizable sugar 3-OMG that is transported via SGLT-1 into the upper small intestine recapitulates the glucoregulatory effect of glucose-sensing 97 , suggesting that upper small intestinal glucose-sensing in inducing GLP-1 release is dependent on the electrogenic capacity of SGLT-1 but independent of cellular glucose metabolism.
Further, the effect of small intestinal glucose sensing on hepatic glucose production regulation is abolished when glucose is co-infused with GLP-1R antagonist exendin-9 97 , strengthening the role of GLP-1 as the mediator of intestinal glucose-sensing on hepatic glucose production Despite the prevalence of carbohydrates in the diet, few studies have investigated the effect of obesity or HFD on intestinal glucose sensing.
In rodents, both diet-induced and genetic models of obesity exhibit reduced satiation in response to intraduodenal carbohydrate infusion, although the effect is less pronounced than what is observed with intestinal lipids and is observed in some but not all studies 57 , Moreover, there are no differences in the response to duodenal infusion of glucose between participants with and without obesity In contrast, obesity is associated with reduced postprandial GLP-1 levels and sensitivity to GLP-1 in rodents , , although gut peptides other than GLP-1 may mediate the anorectic effect of intestinal carbohydrates Despite these unknowns, research with human participants suggests that the incretin effect is impaired in diabetes, which is likely due to reduced GLP-1 secretion and impaired potency of GLP-1 to induce insulin secretion Similarly, HFD in rodents impairs the ability of upper small intestinal glucose infusion to lower glucose production, likely due to reduced GLP-1 secretion This reduction in GLP-1 secretion during HFD is associated with decreased upper small intestinal SGLT-1 levels In line with this, HFD reduces SGLT1 expression in small intestinal L-cells, resulting in impaired GLP-1 response to glucose in primary cultures Fig.
High protein diets in both humans and rodents reduce body weight and adiposity in association with intestinal protein sensing-related increases in gut peptide levels. In humans, duodenal infusion of whey protein hydrolysate decreases food intake without a change in subjective appetite ratings , but in parallel to increased GLP-1 and CCK levels , In addition, casein infusion into the ileum of humans also decreases food intake, whereas infusion into the duodenum or jejunum has minimal effect.
This is possibly explained by the fact that ileal casein infusion resulted in the greatest rise in GLP-1 levels compared to duodenal or jejunal infusion In rodents, various protein solutions potentially reduce food intake more potently than isocaloric and isovolumetric carbohydrate infusions , and the underlying mechanisms may involve CCK release and subsequent activation of CCK-1R on vagal afferent neurons , , , although GLP-1R signaling was not investigated.
Thus, future studies are needed to more definitively identify the specific effects of different types of protein and the intestinal site of protein sensing on the regulation of food intake and gut peptide release. High protein diets improve glucose homeostasis in both rodents and humans , , even in the absence of weight loss in patients with diabetes or during pair-feeding in rodents , In humans, duodenal whey protein hydrolysate impacts circulating glucose, insulin, and glucagon , , while duodenal, jejunal, or ileal casein infusion leads to a substantial increase in insulin levels with no change in glucose Moreover, infusion of leucine alone into the duodenum dose-dependently increases insulin, with slight decreases in glucose, but no change in glucagon These effects are mediated by peptide transporter-1 PepT1 , a di- and tri-peptide proton-coupled transporter located in the brush border membrane of the intestinal epithelium Fig.
Recent evidence using isolated intestinal perfusion technique indicates that dietary protein induces gut peptide secretion via transport of oligopeptides into cells via PepT1. Cellular oligopeptides are broken down into individual amino acids that are released to the basolateral side of the intestine to activate amino acid receptors Taken together, these data indicate that both apical PepT1 and basolateral CaSR could be critical for peptone-mediated GLP-1 release Fig.
Nonetheless, more work is needed to determine the exact mechanism linking intestinal protein sensing to gut peptide release, and which specific amino acids and sensors are required. In contrast to lipids and carbohydrates, sensitivity to intestinal protein-sensing appears to be maintained during obesity, highlighting the potential of protein-sensing as a therapeutic target for weight loss.
There are no differences in energy intake or CCK and GLP-1 responses between individuals with and without obesity following intraduodenal whey protein infusion In line with this data, rats fed an HFD for either 3 or 28 days, with the latter resulting in increased adiposity, still responded to small intestinal casein infusion by lowering hepatic glucose production In addition, high protein intake improves metabolic outcomes, like body weight, adiposity, insulin sensitivity, and food intake, in both rodents and humans , , , and improves glucose tolerance and lowers blood glucose levels in patients with diabetes This may be explained by the fact that intestinal proteins more potently stimulate gut peptide secretion as compared to isocaloric lipids or carbohydrates Future research is warranted to uncover the mechanisms of how intestinal protein sensing, but not lipid or carbohydrate sensing, is maintained during metabolic dysregulation.
Changes in the gut microbiota affect obesity and related metabolic disorders, and the mechanisms linking the gut microbiota to energy and glucose homeostasis have been extensively reviewed , However, the majority of the studies have focused on the role of the microbiota in the large intestine, and few studies have examined the metabolic impact of the small intestinal microbiota.
While there are several orders of magnitude greater abundance of bacteria in the large intestine than in the small intestine, nutrient-sensing, and gut—brain feedback mechanisms are localized to the small intestine, as nutrient absorption limits ingested macronutrients from reaching the large intestine.
Further, the protective barrier of a mucus layer in the small intestine is much less established , allowing for an increased potential for intimate interactions between the host epithelial cells and the gut bacteria.
For example, restoring the gut microbiome in germ-free mice results in an acute, transient phase, followed by a homeostatic phase that impacts jejunal transcriptomics and metabolomics involved in lipid and glucose metabolism and uptake However, the initial acute response is not observed in the ileum or colon, highlighting the sensitivity of the upper small intestine to the microbiome.
Evidence suggests that the microbiota could also greatly impact nutrient-sensing mechanisms. First, microbial metabolites, especially short-chain fatty acids SCFAs , are known to induce gut peptide secretion from EECs , Most bacterially derived metabolites like SCFAs are produced predominantly in the distal intestine but are also present in small amounts in the ileum and can reduce glucose production via a gut—brain axis , Other metabolites, like indole, are highly abundant in the small intestine and also regulate GLP-1 release from EECs Secondly, the gut microbiota impacts EEC physiology.
For example, isolated cells expressing GLP-1 obtained from germ-free and conventional mice exhibit different transcriptomes, which is rapidly altered after only one day of microbiome colonization, suggesting a more direct effect of the bacteria on the EECs vs.
an indirect effect from altered physiology of the germ-free model Further, intestinal expression and circulating levels of gut peptides are altered in germ-free mice , Similarly, HFD converts zebrafish EECs into a nutrient-insensitive state dependent on gut microbiota, as germ-free zebrafish are resistant to the induction of EEC nutrient-insensitivity while an Acinetobacter strain was able to induce EEC nutrient-insensitivity In line with this, bacterial species directly influence GPR, a receptor linked with lipid-induced gut peptide secretion, and GLP-1 expression in vitro Third, LPS, a bacterial byproduct, blunts vagal activation by intestinal nutrients, leptin, or CCK , Thus, there exists a precedent for the ability of small intestinal microbiota to impact nutrient-induced small intestinal gut—brain signaling Fig.
We put forward a working hypothesis for the mechanistic links between small intestinal nutrient-sensing, microbiota, peptide release, and metabolic regulation.
Bacterial by-products such as LPS can impair lipid and glucose sensing and potentially disrupt ACSL3 and SGLT1 dependent pathways that regulate glucose and energy homeostasis. Bile salt hydrolase of bacteria contributes to the bile acid pool and regulates bile acid metabolism. As a result, changes in bile acids can alter GLP-1 release and metabolic regulation via intestinal FXR and TGR5 signaling.
High-fat feeding reduces the abundance of small intestinal Lactobacillus species e. gasseri and consequently inhibits ACSL3 expression and impairs lipid sensing. Lastly, metformin increases the abundance of upper small intestinal Lactobacillus and enhances SGLT1 expression and glucose sensing, while also reducing the abundance of Bacteroides fragilis that results in ileal FXR inhibition and improvement in glucose metabolism.
Bariatric surgery enhances small intestinal nutrient sensing mechanisms and consequently lowers glucose levels, while changes in bile acid metabolism and FXR are necessary for the glucose-lowering effect of bariatric surgery.
In parallel, gut microbiota alters the bile acid pool and thereby potentially affects nutrient sensing and glucose and energy homeostasis. Conjugated bile acids are produced in the liver and released into the duodenum, where they are either absorbed or de-conjugated by the bile salt hydrolase of bacteria.
Bile acids act as signaling molecules in the intestine and elsewhere, binding to FXR and G protein-coupled receptor 19 also known as TGR5 Most, but not all, studies indicate that inhibition of intestinal FXR improves energy and glucose homeostasis , and FXR signaling represses transcription of GLP-1 and inhibits GLP-1 release from L-cells Interestingly, TGR5 signaling increases GLP-1 release from L-cells , thus complicating the role of bile acid signaling in the intestine Fig.
HF-feeding, obesity, and diabetes are all associated with unique microbial profiles in the large intestine. However, evidence suggests that HF-feeding also alters the composition of small intestinal gut microbiota.
In rodents, the majority of the small intestinal bacteria are Lactobacillius , and HF-feeding results in a drastic reduction in the relative abundance of this genus 45 , Recent work indicates that altered small intestinal microbiota during HFD drives impairments in intestinal lipid-sensing, as the transplant of the small intestinal microbiota of short-term HF fed rats into chow-fed rats abolished the ability of small intestinal lipid infusion to improve glucose tolerance and lower hepatic glucose production.
Treatment of HF-fed rats with a small intestinal infusion of Lactobacillus gasseri enhances upper small intestinal lipid-sensing, via restoration of long-chain acyl-CoA synthetase ACSL3 gasseri exhibits bile salt hydrolase activity and can thus alter the composition of the bile acid pool.
Small intestinal L. gasseri increases ACSL3 and subsequent lipid-sensing through a mechanism dependent on reduced FXR signaling. These findings are consistent with the fact that bile acid sequestrants i.
Recent evidence-based on studies with the anti-diabetic medicine metformin indicate that the glucoregulatory impact of intestinal glucose-sensing is mediated by the small intestinal microbiota.
While metformin directly influences hepatic metabolism , as an orally administered drug metformin concentrations in the small intestine are much greater than in the serum Oral metformin reduces blood glucose levels more than intravenous or portal vein administration , demonstrating a role for intestinal-mediated mechanisms of action in improvements in glucose homeostasis.
Pretreatment of HF-fed rats with metformin restores the ability of upper small intestinal glucose infusion to lower glucose production via increased portal vein GLP-1 levels and small intestinal SGLT-1 expression and in parallel changes the composition of small intestinal microbiota This is in line with several other studies that highlight the importance of the gut microbiota in mediating the beneficial effects of metformin , In addition, individuals with newly diagnosed diabetes treated with metformin for three days exhibit alterations in the gut microbiota including increased Lactobacillus and reduced Bacteroides fragilis abundance, which result in inhibition of FXR signaling to improve glucose metabolism This observation is similar to the ability of L.
gasseri to increase intestinal lipid-sensing to improve glucose homeostasis via FXR 45 Fig. Collectively, these studies highlight small intestinal nutrient-sensing mechanism mediates the beneficial effects of metformin through changes in gut microbiota and bile acids. Evidence is emerging on the impact of the small intestinal microbiota also in the efficacy of gastric bypass.
Despite extensive evidence of an overall role of the large intestinal microbiota in mediating the effects of bariatric surgery , at least one study demonstrated that gastric bypass alters the microbiota of the duodenum, jejunum, and ileum In addition, while the jejunal nutrient-sensing mechanism at least partly mediates the beneficial effects of duodenal—jejunal bypass surgery on glucose homeostasis 98 , the glucose-lowering effect of vertical sleeve gastrectomy is dependent on both the gut microbiota and bile acid signaling Fig.
While technological advancements begin to detail the role of intestinal nutrient-sensing in gut—brain neuronal signaling, they concurrently expand the field. One example of this is the use of single-cell RNA sequencing to understand vagal afferent signaling.
Several groups distinctly labeled nodose ganglion neurons according to their expression profile, however, the results are expansive and sometimes contradictory 44 , Based on these studies, vagal afferent neurons containing GLP-1R have no impact on intestinal nutrient-sensing mechanisms, which are instead regulated by GPRpositive neurons Indeed, various neurons terminating in the intestinal mucosa, that likely sense gut peptides released in response to intestinal nutrients, have no effect on food intake, and only direct activation of a subset of IGLE neurons that detect intestinal stretch and not gut peptides suppresses food intake A subset of EECs called neuropods exist that directly synapse with vagal neurons, and rapidly signal via glutamate to the nucleus of the solitary tract in a single synapse to relay initial spatial and temporal information about the meal that could later be followed by more traditional gut peptide signaling Despite these interesting and exciting advances and the discovery of new nutrient sensory cells, the exact neurons that mediate the gut—brain signaling and nutrient sensing in regulating metabolism are complex and warrant future investigations.
Future studies are needed to start teasing apart these complexities, while also integrating the gut microbiota and metabolites into the picture. For instance, while the gut microbiota can impact EECs, it is plausible that vagal afferents themselves can be impacted by bacterial metabolites In contrast to energy intake, the impact of nutrient-induced gut—brain vagal signaling on energy expenditure has been poorly characterized.
Intestinal lipids regulate brown fat thermogenesis via vagal afferents and possibly via GLP-1R signaling , and vagal knockout of the transcription factor peroxisome proliferator-activated receptor-γ, which is activated by fatty acids and could thus be involved in lipid-sensing, affects thermogenesis Likewise in humans, intraduodenal infusion of intralipid increases resting energy expenditure Nutrient infusions into the duodenum of rats modulate energy expenditure Future work is needed to detail the connections between nutrient-sensing mechanism, gut microbiota, and impact on energy expenditure via thermogenesis in brown or browning white adipose tissue Overall, extensive evidence indicates that targeting nutrient sensing in the small intestine impacts energy and glucose homeostasis during normal physiology and in the context of obesity and type 2 diabetes.
Given the distinct effects of HFD and obesity on the diminution of nutrient-sensing dependent gut—brain pathways, future studies examining the gene and environmental interactions are warranted to further the development of personalized medicine approaches. Similarly, the expansive role of the gut microbiota in host metabolic health further highlights the need for personalized approaches to treating metabolic diseases.
As such, studies in humans and rodents beginning to unravel the interactions between the gut microbiota, small intestinal EECs, and vagal signaling, are laying the groundwork for the development of therapeutics targeting small intestinal nutrient sensing to treat obesity and type 2 diabetes.
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Nutrients Natural prevention of ulcers needed for the nutrien functioning of Metabolic support for nutrient absorption body. Nytrient foods rich in vitamins and minerals such absorpyion Vitamin C, Vitamin Eating disorder causes, B-complex Red pepper hash, iron, and calcium is not Metaoblic. Right from how you pair your foods to Metsbolic you eat them, there are numerous ways that can impact the way the body absorbs the nutrients. This is why even if you are eating nutrient-rich foods, you might not be getting all the nutrients. So to help you reap the benefits of nutrients here are ways to improve nutrient absorption through foods. How you combine your foods can play a major role in the absorption of nutrients. Pairing foods wisely can increase the nutrient absorption and also promote the overall health.Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to Mftabolic browser or turn off compatibility mode in Internet Explorer.
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Absorptuon nutrients trigger feedback mechanisms to prevent postprandial energy excess by suppressing food intake and endogenous nutrient production Fig.
In addition to GLP-1 and CCK, EECs secrete up to 20 varieties of gut peptides that decrease energy intake and regulate glucose homeostasis.
However, we will herein focus mostly on GLP-1 and CCK, the most studied small intestinal gut peptides that target the vagal afferents, brain, and pancreas to regulate energy and glucose homeostasis.
Although the post-prandial feedback mechanisms are partly coordinated by direct interaction of the liver, pancreas, and brain with circulating nutrients 678nutrient-induced small intestinal signaling mechanisms drive a majority of this feedback.
This is attributed to the glucoregulatory effect of GLP-1 and another gut peptide glucose-dependent insulinotropic polypeptide GIPin which the peptides are released from the small intestine in response to glucose sensing Recently, the role of the upper small intestinal GLP-1 secreting cells is highlighted by selectively knocking out Gcg expression a gene from which GLP-1 is derived in the lower gut ileum and large intestine In response to oral glucose challenge, distal Gcg knockout mice responded with normal levels of secreted plasma active GLP-1, thereby unveiling the importance of upper small intestinal GLP-1 secreting cells in glucose-sensing Small intestinal-derived peptides act in an endocrine fashion on the peripheral and CNS targets or in a paracrine fashion on vagal afferent neurons.
These neurons are in close proximity to the gut, contain receptors for GLP-1, CCK, and peptide YY PYY and terminate in the nucleus of the solitary tract of the hindbrain where it has been demonstrated to regulate energy and glucose homeostasis Alternatively, gut peptides may activate the enteric nervous system to relay information to the vagal afferent terminals via glutamate or nitric oxide 1819although the difficulty in targeting enteric neurons per se in vivo has limited the understanding of the role of the enteric nervous system in mediating the effects of nutrient-sensing.
Nevertheless, the role of gut—brain vagal signaling pathways in metabolic homeostasis is demonstrated by the fact that chemical, surgical, genetic, or viral manipulation of the vagal gut—brain pathway impairs nutrient-induced regulation of energy and glucose homeostasis.
This is reviewed in detail elsewhere GLP-1R is expressed in the vagal afferent neurons, pancreas, and the brain Knockdown of the GLP-1R in vagal afferent neurons via lentiviral injection into the nodose ganglia the inferior ganglion of the vagus nervewhich enables knockdown throughout the vagus nerve, increases meal size and postprandial glycemia, and blunts insulin release 22 while knocking down GLP-1R via the use of transgenic mice in the gut—brain neuronal axis leads to increased glucose levels In addition to the gut—brain metabolic axis governed by the glucose sensing in the small intestine, glucose sensing in the portal vein can be triggered by intestinal gluconeogenesis induced by protein and fiber intake and activate a portal vagal—brain axis to regulate glucose and energy homeostasis Overall, nutrient-sensing in the small intestine plays a major role in gut—brain negative feedback signaling that regulates energy and glucose homeostasis Fig.
Small intestinal lipid sensing suppresses food intake through the release of CCK and GLP-1 and the activation of vagal afferents. It is traditionally believed that lipid sensing in the small intestine occurs on the apical luminal side where long-chain fatty acids LCFA are absorbed and metabolized to generate sensory anorectic signals.
The Intralipid effect is blocked by the local anesthetic tetracaine, which inhibits nerve impulses, indicating small intestinal vagal innervation as a mediator of the anorectic signals Further, co-infusion of lipid with a lipase inhibitor blocks the ability of lipid to suppress food intake, as well as increase CCK and GLP-1 Inhibition of chylomicron formation with Pluronic L attenuates the anorectic effect, celiac and cervical vagal afferent activation, and gut peptide release induced by lipids 33 Similarly, infusion of fatty acids with a chain length of less than C10 which do not assemble in chylomicrons but directly diffuse out of enterocytes fails to reduce energy intake and increase CCK levels in humans These observations argue against the traditional view of lipid sensing that occurs on the apical luminal side of the small intestine, prior to absorption.
Indeed, despite studies that elucidated the role of the receptor GPR40 and GPR to a lesser extent in mediating LCFAs to stimulate gut peptides release 36the cellular site of action apical vs. basolateral has not been fully elucidated.
Recently, utilizing an isolated intestinal perfusion model, it was shown that linoleic acid and GPR40 agonists induce GLP-1 release only when infused into the vasculature that would target the basolateral side, and not to the apical lumen In cultured, stable, immortalized murine EECs GLP-1 secretion is dependent on lipoprotein lipase to hydrolyze chylomicrons and on GPR40 to bind the liberated LCFAs 38further supporting that activation of EECs by LCFAs occurs on the basolateral side through hydrolysis of newly synthesized chylomicrons.
Additionally, CD36 a protein that transports fatty acids into cells and is documented to mediate chylomicron formation 39 knockout mice have impaired CCK release and fail to suppress food intake in response to duodenal lipids 4041indicating that chylomicron formation in the small intestine is necessary for lipid sensing to lower food intake and thereby supporting the basolateral sensing hypothesis Fig.
a Mechanisms of small intestinal lipid sensing. The hydrolysis of chylomicrons by nearby enterocytes on the basolateral membrane may lead to increased LCFAs that can activate basolateral GPR40 to induce peptide release.
b Mechanisms of small intestinal carbohydrate sensing. However, ileal glucose sensing may stimulate the release of GLP-1 independent of SGLT1. In response to high-fat feeding or obesity, small intestinal SGLT1 expression is reduced, leading to an impairment of glucose sensing, GLP-1 secretion, and glucose control.
c Mechanisms of small intestinal protein sensing. Luminal small oligopeptides and amino acids are taken up by PepT1 and amino acid transporters, respectively, into the enterocyte and enteroendocrine cells. Small intestinal protein sensing stimulates the release of CCK and GLP-1 and regulates feeding and glucose homeostasis potentially via PepT1 dependent mechanisms.
In addition, amino acids stimulate peptide release via the membrane-bound calcium-sensing receptor, the umami taste receptor, and G-protein-coupled receptor 6A. However, the downstream mechanism mediating the peptide release remains elusive.
In parallel, amino acids are also transported to the basolateral side, and studies implicated that they may activate the calcium-sensing receptor to stimulate GLP-1 secretion.
Vagal afferent fibers mediate the anorectic effects of intestinal lipid-sensing and are activated by several gut peptides Vagal afferents contain CCK-1 receptor CCK-1R and selective knockdown of CCK-1R in vagal afferents abolishes the ability of CCK to lower food intake However, the impact of vagal CCK-1R on small intestinal lipid-induced CCK signaling has not been established Vagal afferents also express GLP-1R 42and at least one study reports that GLP-1 signaling mediates the suppressive effects of jejunal linoleic acid infusion However, GLP-1R-expressing vagal afferent neurons were also reported to detect stomach and intestinal stretch but have no impact on nutrient-sensing Thus, the effect of GLP-1R on intestinal lipid sensing remains unclear.
It is possible that the enteric nervous system, which contains GLP-1R, may mediate the gut—brain effect instead 18 Utilizing pancreatic—euglycemic clamps with plasma insulin levels maintained at a basal non-stimulated condition, upper small intestinal lipid infusion lowers hepatic glucose production In contrast, a study with human participants reports that during the pancreatic—euglycemic clamps, no difference in glucose production is detected in response to intraduodenal infusion of lipid vs control group However, this observation is made in the presence of a progressive rise in plasma insulin and glucose levels prior to the start of the lipid or control infusion, and a parallel progressive drop in both plasma free fatty acids and glucose production in both groups Thus, it is not surprising that glucose production is not further lowered by intraduodenal lipid vs.
saline infusion in a state that mimics the postprandial state, in which hepatic glucose production is already inhibited. Similar to lipid-induced reductions in food intake, the ability of small intestinal lipid infusion to lower hepatic glucose production is dependent on CCK and GLP-1 signaling during the pancreatic basal insulin -euglycemic clamps 45 Further, inhibiting CCK-1R signaling during refeeding, which activates nutrient-sensing pathways, results in postprandial hyperglycemia The specific mechanisms leading to the release of CCK and subsequent effects on glucose homeostasis are not fully understood, although the esterification of fatty acids to fatty acyl-CoA via acyl-CoA synthetase and the subsequent activation of mucosal protein kinase C PKC -δ are necessary for rats 46 This is consistent with the fact that LCFA induces CCK release in intestinal secretin tumor cells via PKC-δ activation In parallel, the formation of chylomicron is also implicated in CCK release 50but the underlying mechanisms of how lipids stimulate CCK to release overall remain elusive Fig.
Further, the specific role of vagal GLP-1R signaling in mediating the glucoregulatory effect of lipids remains to be clarified. In addition to lowering hepatic glucose production via a gut—brain axis 4546small intestinal lipid-sensing could regulate glucose homeostasis via GLPinduced increase in insulin or suppression of glucagon secretion, as lipid-sensing increases GLP-1 release 45.
However, GLP-1 induced increase in insulin secretion requires the presence of elevated circulating glucose levels Thus, it is possible that while an infusion of lipid alone increases GLP-1, this would not substantially elevate plasma insulin levels in the absence of a concomitant rise in blood glucose levels, as reported in human studies 52 Despite this, increasing circulating active GLP-1 levels during an Intralipid intestinal infusion via DPP-IV inhibition inhibits degradation of GLP-1 decreases glucose and increases insulin levels In addition, while GLP-1 is known to suppress glucagon secretion, glucagon is consistently increased with Intralipid infusion 52 Although it has not been evaluated, this unexpected effect of Intralipid on glucagon could be due to the concurrent CCK release, as CCK lowers the inhibitory effect of glucose on glucagon secretion A high-fat diet HFD impairs lipid-induced gut—brain feedback regulating both energy and glucose homeostasis.
Intestinal sensing of lipids is impaired during HFD in both rodents and humans 55however, it is still contentious as to whether this is due to chronic exposure to HFD or induction of obesity.
For example, studies in rats have shown that the combination of an HFD with a genetic background that is predisposed to obesity, is associated with reduced intestinal-lipid sensing 56 ,
: Metabolic support for nutrient absorption| Metabolic support in the critically ill: a consensus of 19 | The balance of microbes at each section of your digestive tract significantly impacts your nutrient status by playing essential roles in the biosynthesis and bioavailability of several micronutrients. There is a bidirectional micronutrient—microbiome axis. The nutrients you consume help to shape the balance of microbes in your gut since they destroy many of these nutrients for growth and survival. In the other direction, your gut microbiota produces significant quantities of a wide range of nutrients. Your microbiome is especially important for the production of vitamin K and B group vitamins. The microbes in your gut also enhance the absorption of minerals such as iron and calcium. You need the right microbes in your microbiome to assist with the digestion of complex carbohydrates and fibers that you cannot digest on your own. This helps absorb essential nutrients and produces short-chain fatty acids SCFAs that help maintain a healthy gut, metabolism, and balanced inflammation. You can support a diverse microbiome by eating an anti-inflammatory diet rich in fiber, fermented foods, and prebiotics like asparagus, garlic, and dandelion greens while limiting processed foods, additives, and refined sugars. In some cases, probiotic supplementation can be added if needed based on stool testing. In some cases, supplements for digestion, like digestive enzymes or bitters, may be necessary to support nutrient absorption and healing. As discussed above, your body needs enzymes from your gastrointestinal tract and its accessory organs to fully break down and absorb nutrients. Certain health conditions result in insufficiency of some of these digestive enzymes. In these cases, taking exogenous replacement enzymes may be necessary to help your GI tract break down and absorb nutrients. For example, exocrine pancreatic insufficiency EPI can develop due to cystic fibrosis, autoimmune diseases like Sjogren's syndrome , and pancreatitis , causing the pancreas to produce too few digestive enzymes. In other cases, a person may have insufficient enzymes needed to digest specific sugars. This can be genetic in conditions like congenital sucrase-isomaltase deficiency or acquired in lactose intolerance caused by acute gastrointestinal infections, small intestinal bacterial overgrowth SIBO , celiac disease, and Crohn's disease. Environmental and lifestyle factors can also impact digestive enzyme production. Excessive alcohol intake, smoking, and chronic stress can all decrease the production of digestive enzymes. Depending on your individual needs, digestive enzymes are available in various forms. Individual specific enzymes like lactase can be taken to target a specific deficiency, or multi-enzyme supplementation containing a variety of enzymes such as amylase, lipase, and protease enzymes can work synergistically. These can be derived from animal sources or come from plants like bromelain from pineapple. Microbe-derived enzymes synthesized from yeasts or fungi are another alternative and generally require lower dosing. Herbs with bitter flavor are also used to support and improve digestion and nutrient absorption. Digestive bitters like ginger, wormwood, gentian, burdock root, dandelion root, and artichoke leaf are taken in your mouth before eating to stimulate the bitter taste buds. This signals your digestive system to start the process of digestion by producing more saliva, gastric juices, and enzymes to optimize digestion and absorption of your food. Studies show that stress has many impacts on digestion and nutrient absorption, is related to functional gastrointestinal disorders such as irritable bowel syndrome IBS , and creates imbalances in the gut microbiome. The activation of the sympathetic nervous system during stress contributes to changes in motility or movement in the gastrointestinal tract. If motility slows, you can have an increased risk of dysbiosis like SIBO. On the other hand, stress can also contribute to increased motility, which impairs nutrient absorption. Stress also increases inflammatory cytokines that damage the intestinal lining and cause impaired nutrient absorption. Studies also show stress -induced changes in the microbiome that lead to dysbiosis and significantly affect the microbiome's functioning. You can adapt your lifestyle for better nutrient absorption in several powerful ways. Mindful eating involves your food and mind-body present moment state with a non-judgmental awareness. This approach has been shown to counter digestive disturbances attributed to stress. Getting adequate restorative sleep is also crucial for digestion and the health of your microbiome. To get at least hours each night, establish a regular sleep routine to go to sleep and wake up at the same time each day and set up your sleep environment to be dark, quiet, and cool. Exercising regularly but not too intensely is also beneficial for digestion and the microbiome. Incorporating mind-body practices like yoga and tai chi can be especially beneficial for calming the mind and nervous system while getting in movement. You need the proper balance of nutrients to maintain optimal health and functioning. Your digestive tract allows you to digest and absorb nutrients you consume in food and supplements when it works properly. The small intestine is the primary source of nutrient absorption and depends on help from the mouth, stomach, liver, gallbladder, and pancreas to adequately digest and absorb nutrients. Health issues that impact these organs, the intestinal surface, the balance of microbes in your gut microbiome , inflammation levels, and more can influence how well you absorb various nutrients. Functional medicine offers a comprehensive multimodal approach to understanding and addressing the underlying factors contributing to poor absorption of nutrients. This allows for a personalized approach incorporating diet, lifestyle, supplementation, and stress management to optimize nutrient absorption and restore balance. Barone, M. Gut microbiome—micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins? BioFactors , 48 2 , — Basile, E. Physiology, Nutrient Absorption. gov; StatPearls Publishing. Bek, S. Association between irritable bowel syndrome and micronutrients: A systematic review. Journal of Gastroenterology and Hepatology , 37 8 , — Blake, K. Anti Inflammatory Diet What to Eat and Avoid Plus Specialty Labs To Monitor Results. Rupa Health. Cherpak, C. Mindful eating: a review of how the stress-digestion-mindfulness triad may modulate and improve gastrointestinal and digestive function. Cloyd, J. Top Lab Test to Run on Your Iron Deficiency Anemia Patients. A Functional Medicine Protocol for Leaky Gut Syndrome. How To Test for Lactose Intolerance. Bile Acids Testing, Interpreting, Treatment. How to Heal Your Gut Naturally With Functional Nutrition. What are Digestive Enzymes: How to Test Your Patients Levels. A Functional Medicine Celiac Disease Protocol: Specialty Testing, Nutrition, and Supplements. The Importance of Comprehensive Stool Testing in Functional Medicine. Macro and Micronutrients Uncovered: Understanding Their Role, Deficiencies, and Clinical Relevance. Cloyd, K. Gut Microbiome Diversity: The Cornerstone of Immune Resilience. Conner, V. Greenan, S. Constant Burping Is A Sign Of This Harmful Bacterial Overgrowth. Guo, Y. Irritable Bowel Syndrome Is Positively Related to Metabolic Syndrome: A Population-Based Cross-Sectional Study. PLoS ONE , 9 11 , e Hadadi, N. Intestinal microbiota as a route for micronutrient bioavailability. Current Opinion in Endocrine and Metabolic Research , 20 , Kielbiski, E. What Are Digestive Enzymes and How Do They Work? Kresge, K. IBS vs IBD: Know The Symptoms. Weight Loss, Diarrhea, And Gas Are Signs Of This Dangerous Condition. How Does Low Stomach Acid Affect Your Body? LoBisco, S. How Food Affects Your Mood Through The Gut-Brain Axis. How To Build A Healthy Microbiome From Birth. There are three primary omega-3 fatty acids: eicosapentaenoic acid EPA , docosahexaenoic acid DHA , and alpha-linoleic acid ALA. While omega-3 fatty acids are found in foods such as fish like salmon and mackerel , walnuts, and flaxseeds, research shows that Americans are not consuming enough of certain omega-3s through diet alone. Increasing omega-3 levels via supplements may be particularly beneficial for people already at a metabolic disadvantage. In one study of overweight middle-aged men, those with the highest blood levels of omega-3s had lower levels of the inflammatory marker CRP, fewer free fatty acids substances that can cause insulin resistance in the blood, and better insulin sensitivity compared to men with the lowest levels of omega-3s. Women need around 1, mg of ALA omega-3s daily, while men need about 1, mg daily. Special considerations: The conversion rate of ALA to EPA and DHA in the body is poor, so supplements containing EPA and DHA, such as fish oil or algae oil, are your best bet and may be better for inflammation. Look for supplements that have undergone molecular distillation , which removes heavy metals and other contaminants that fish can absorb. Metabolic benefit: Selenium is an essential trace mineral that supports normal thyroid function and packs an antioxidant punch , both of which are crucial for optimal metabolic health. Within the body, selenium is incorporated into the structure of specific proteins, creating around two dozen selenoproteins , which influence various processes. For example, several selenoproteins help neutralize free radicals and protect cells from the oxidative damage that often underlies insulin resistance and metabolic dysfunction. Selenium content of food can vary by region depending on soil quality. In general, U. soil contains enough selenium for most individuals to meet the RDA of 55 mcg—however, some research suggests there may be metabolic benefits of supplementing with additional selenium though other studies show a link between high selenium and Type 2 diabetes. Selenium is also found in high concentrations in the thyroid, a gland that produces hormones T3 and T4 that regulate cellular metabolism throughout the body; as a result, thyroid hormones regulate things like body weight, temperature, and organ function. Selenium exerts a protective effect on the thyroid by helping neutralize the many free radicals generated during thyroid hormone production. This means too little selenium may contribute to thyroid hormone imbalances and thyroid disorders that compromise metabolic function. How much should you take? The RDA for selenium is 55 mcg per day for adults. Research on higher amounts is mixed , but some studies suggest that mcg per day may support optimal thyroid and metabolic health. Special considerations: Early signs of excess selenium intake include a metallic taste in the mouth and garlic breath. If you notice either of these, you most likely need a lower dose. Each nut contains mcg of selenium. Metabolic benefit: Zinc is an essential mineral that activates enzymes needed for hundreds of vital biochemical reactions in the body, including those that regulate vitamin D activation and thyroid function. Zinc also serves as an antioxidant by influencing enzymes that neutralize free radicals or reactive oxygen species that might otherwise trigger cellular damage and insulin resistance. Found in high amounts in pancreatic beta cells insulin-secreting cells , zinc is vital for the proper synthesis, storage, and release of insulin—the hormone that helps transport glucose from the bloodstream into cells where it can be used for energy or storage. Zinc deficiency, while somewhat rare in the U. A meta-analysis of 32 interventional studies found that zinc supplementation significantly reduced fasting blood glucose, HbA1c, and inflammatory markers among people with Type 2 diabetes or at risk for diabetes. The RDA for zinc is 8 mg daily for women and 11 mg daily for men. You can supplement with a bit more than this, but the beneficial cap for metabolic benefits may be around 25 mg per day. Studies have also shown that excessive zinc intake may lead to elevated HbA1c and high blood pressure, so stay below the upper limit of 40 mg per day unless your healthcare provider suggests otherwise. Special considerations: Zinc may interfere with a few medications , including certain antibiotics. Zinc can also impact copper absorption, so long-term zinc supplementation should include copper some products combine the two. In addition, it helps regenerate other antioxidants, like vitamin E, in the body. In one study , supplementing with 1, mg of vitamin C per day significantly reduced fasting blood glucose, along with the inflammatory proteins interleukin-6 and CRP, in obese patients with diabetes or high blood pressure. While overt vitamin C deficiency is rare, someone may experience inadequate intake if they get a limited variety of fruits and vegetables or have certain gastrointestinal conditions. In one small study , researchers measured blood levels of three classes of POPs in 15 healthy women, both before and after supplementing with 1, mg of vitamin C per day for two months. The result: Several chemicals classified as organochlorine pesticides OCPs and polychlorinated biphenyls PCBs were significantly reduced after vitamin C supplementation. Research suggests that vitamin C might help lower levels of uric acid a natural waste product from the digestion of foods in the body. In a meta-analysis of 16 studies, supplementing with vitamin C at doses ranging from , mg per day was associated with significant reductions in uric acid levels among people under The RDA for vitamin C is 75 mg per day for women and 90 mg per day for men. However, the research above suggests that higher doses, ranging from , mg per day, are likely safe and may offer metabolic benefits. Special considerations: For those with kidney stones or who are predisposed to forming stones, we recommend speaking with your physician before considering taking vitamin C, as there is a potential risk that it can contribute to developing certain types of stones. For most people, vitamin C is relatively safe and has a low risk for toxicity and side effects if you stay under the upper limit of 2, mg daily. If you consume too much, you may experience gastrointestinal distress, such as diarrhea, nausea, and cramping. Metabolic benefit: Coenzyme Q 10 CoQ 10 is a powerful antioxidant found in cells throughout the body, most abundantly in the heart, liver, and kidneys. As an antioxidant, CoQ 10 also helps neutralize free radicals that might otherwise contribute to metabolically damaging oxidative stress. Conditions such as atherosclerosis, nonalcoholic fatty liver disease NAFLD , and metabolic syndrome are characterized by increased inflammation and oxidative stress—which is why boosting CoQ10 levels via supplementation may be beneficial. CoQ 10 levels also start falling around age 20 and may be as little as half in certain parts of the body by Supplementing with CoQ 10 appears beneficial and has been associated with improvements in several metabolic biomarkers. In one study , supplementing with mg of CoQ 10 per day for 12 weeks was associated with reductions in fasting blood glucose, insulin resistance, and LDL cholesterol and increased HDL cholesterol among women with Type 2 diabetes. And another study found that supplementing with mg per day for four weeks significantly improved waist circumference and markers of oxidative stress among people with NAFLD. CoQ 10 supplementation has also been shown to improve blood glucose levels and insulin resistance among women with polycystic ovarian syndrome PCOS —a condition associated with insulin resistance, weight gain, and increased risk of Type 2 diabetes. Higher doses up to mg per day also appear safe but may not be necessary. Special considerations: CoQ10 is fat-soluble , so take supplements with a fat-containing meal or snack to boost absorption. CoQ10 is relatively safe, and no serious side effects have been reported; however, some people may have mild side effects such as digestive upset and insomnia. It may also interfere with medications like insulin or blood-thinning drugs like warfarin. Additionally, certain supplements and medication combos can be problematic or require you to carefully time your doses for example, magnesium and antibiotics. For these reasons, supplementation should be personalized. Start by talking to your healthcare provider about your current health, diet, and lifestyle to help determine which of the above supplements or others may be appropriate. To further hone your ideal supplement lineup, consider seeking a functional medicine physician or dietitian who can order appropriate nutrient lab testing to see where you may be lacking. Once you know what vitamins and supplements you want to take, your next goal is to pick a high-quality, reputable brand. This is important because research shows that several low-quality supplements have been contaminated or adulterated with harmful bacteria, fungi, heavy metals, and even prescription drugs. The FDA typically only investigates and removes supplements after complaints from customers or healthcare professionals are made. To find a good supplement, ask for brand recommendations from a healthcare provider who is knowledgeable about supplements; ideally, seek out supplements that have been third-party tested by an independent organization such as NSF International or U. Pharmacopeia l Convention USP. Some highly-rated, well-established brands that offer third-party testing on all or some of their products include Pure Encapsulations , Thorne Research , and Integrative Therapeutics. Additionally, CVS recently became the first national retailer to require third-party testing for all vitamins and supplements sold in its stores and online. Low calcium levels have been associated with impaired insulin release, while other studies show an association with less insulin resistance. A study analyzing health data over 10 years found an association between calcium supplements and plaque buildup in the arteries. There are also certain stress relief supplements you can consider taking. There are a number of reasons that you may want to help improve nutrient absorption. In some cases, taking digestive enzyme supplements may help your body absorb nutrients. Ideally your supplement will also include botanicals and herbs that further support digestive health, such as fermented, whole-food ingredients like organic black pepper fruit, organic ginger root, turmeric root and apple cider vinegar. You can take one serving with your heaviest meal to aid with digestion and balance of healthy microflora. This depends on the specific nutrient and how you acquire it for example, pill form versus food form. Meals that are very high in fiber, protein and fat typically take longer to fully digest and absorb than those high in simple sugars and carbs. As soon as you eat something, digestion starts to take place inside the mouth, and it continues for hours. Most nutrients will make their way through the stomach and to the small intestine within about 6 to 8 hours of consumption. Most of the absorption happens in that area, while some happens later in the large intestine. How can you improve nutrient absorption? Jill Levy has been with the Dr. Axe and Ancient Nutrition team for seven years. She completed her undergraduate degree in Psychology from Fairfield University, followed by a certification as a Holistic Health Coach from the Institute for Integrative Nutrition. A chia seed pudding is one of those healthy snacks that many of us, truth be told, have yet to make. Perhaps a chocolate version will convince you to give it a try? Strawberries make a great flavor for so many desserts, such as strawberry shortcake. You have a delicious lunch, go back to work but suddenly start yawning. What is going on? But what types of circumstances can lead to occasional dark circles, including occasionally not getting enough sleep? Your Cart is Currently Empty. Shop All. Learn Take the Quiz. Best Sellers. Regenerative Organic Certified® New! View All. Shop by Category Collagen. Shop by Focus Everyday Health. Shop Collagen Get clinically proven results for your hair, skin, nails, joints and gut with collagen. View All Collagen Products. |
| Navigating Nutrient Absorption: Functional Medicine for Optimal Digestion | People who nutriejt at high Metaboilc Protein for injury prevention in athletes hutrient related to mineral deficiencies, Healthy snack ideas as osteoporosis with calcium deficiency Protein for injury prevention in athletes ahsorption with iron deficiencymay wish to monitor their food choices for anti-nutrient content. Inside Levels Announcement Announcing: Dr. Unfortunately, proper nutrient absorption may be a growing concern, especially among the elderly, and even those dealing with unrelenting stress. Always inform your doctor about any dietary changes that are made for health reasons. Vincent Giampapa. Wondering what percentage of a multivitamin is absorbed? Flowers, chocolates, organ donation — are you in? |
| References and Recommended Reading | Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial. Learn More. Article CAS PubMed PubMed Central Google Scholar Claessens, M. Free Healthbeat Signup Get the latest in health news delivered to your inbox! Journal of Gastroenterology and Hepatology , 37 8 , — |
| 5 Simple Tips To Improve Nutrient Absorption From Foods - Tata 1mg Capsules | This is consistent with Metabolic support for nutrient absorption fact that LCFA induces CCK release in abxorption secretin tumor cells via PKC-δ activation Lavoisier and the Chemistry of Life. Diabetes Care 42— American journal of physiology. Plant physiology. |
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