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Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions
Abstract and Figures
Glutamine, a conditionally essential amino acid, is consumed predominantly in the gastrointestinal tract as a source of energy, particularly under the conditions of trauma, sepsis and surgery. In this article, we discuss the unique role of glutamine in the preservation of epithelial barrier function in the gastrointestinal tract. Glutamine supplementation protects the gastrointestinal mucosal homeostasis during total parenteral nutrition, diarrhea, radiation injury, starvation, sepsis and trauma. A significant body of evidence indicates that glutamine preserves the gut barrier function and prevents permeability to toxins and pathogens from the gut lumen into mucosal tissue and circulation. Recent studies demonstrated that the mucosal barrier protective effect of glutamine relates to its effect on preservation of epithelial tight junction integrity. The current understanding of glutamine-mediated protection of intestinal epithelial tight junction integrity and the potential mechanisms involved in this protective effect of glutamine are discussed.
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... Several studies have demonstrated the beneficial effects of BCAA supplementation on the development of villi (Chang et al., 2015;Allameh and Toghyani, 2019). Additionally, BCAA provides the amino groups for the synthesis of glutamine, which is considered the major fuel source for epithelial cells to maintain the gut barrier functions (Wu, 2009;Rao and Samak, 2012). Branched-chain amino acids have also been reported to be an important energy source for immune cells (Fan et al., 2015;Nie et al., 2018), and given the high dependence of the immune system on protein synthesis for producing cytokines, immunoglobulins, immune cells, and other immune molecules (Calder, 2006;Li et al., 2007), BCAA are also considered essential for normal immune functions (Bifari and Nisoli, 2017). ...
We investigated the effects of supplementing arginine (Arg) and branched-chain amino acids (BCAA) in broilers fed reduced-protein diets and challenged with Eimeria spp. All birds were fed the same starter diet meeting Cobb 500 nutrient specifications from d 1 to 9. Four grower diets: positive control (PC) with 20.0% crude protein (CP); reduced-protein negative control (NC) with 17.5% CP; or NC supplemented with Arg or BCAA at 50% above recommendations (ARG or BCAA) were fed to the birds from d 9 to 28. Birds were allocated in a 2 × 4 factorial arrangement (4 diets, each with or without challenge), with 8 replicates per treatment. On d 14, the challenge groups were orally gavaged with mixed Eimeria spp. Intestinal permeability was higher (P < 0.05) in NC than PC, whereas the permeability of ARG and BCAA groups did not differ significantly from PC. On d 28, a significant interaction (P < 0.01) was observed in CD8+: CD4+ ratios in cecal tonsils (CT), Eimeria challenge increased the ratios in all groups except for the ARG group. On d 21, a significant interaction was found for CD4+CD25+ percentages in CT (P < 0.01) that Eimeria challenge increased the percentages only in PC and NC groups. On d 21 and 28, significant interactions (P < 0.01) were found for macrophage nitric oxide (NO) production. In nonchallenged birds, NO was higher in the ARG group than other groups, but in challenged birds, NO was higher in both ARG and BCAA groups. On d 21, a significant interaction was found for bile anticoccidial IgA concentrations (P < 0.05) that Eimeria challenge increased IgA only in NC and ARG groups. The results suggest that a reduced-protein diet exacerbates the impact of the Eimeria challenge on intestinal integrity, but this could be mitigated by Arg and BCAA supplementations. Arginine and BCAA supplementations in reduced-protein diets could be beneficial for broilers against Eimeria infection by enhancing the immune responses. The beneficial effects of Arg supplementation tended to be more pronounced compared to BCAA supplementation.
... l-Glutamine, quercetin, slippery elm bark, marshmallow root, N-acetyl-d-glucosamine (NAG), licorice root, maitake mushrooms, and zinc orotate have shown potential benefits through gut microbiota and intestinal barrier functions. l-Glutamine can protect intestinal epithelial tight junctions (Rao and Samak, 2012). Likewise, quercetin assembles zonula occludens-2, occludin, and claudin-1 (Suzuki and Hara, 2009), and slippery elm bark assists in tightening the epithelial junctions in the intestinal walls (Ried et al., 2020). ...
l-Glutamine, quercetin, slippery elm bark, marshmallow root, N-acetyl-d-glucosamine, licorice root, maitake mushrooms, and zinc orotate have been reported to help treat leaky gut. The purpose of this research was to explore the impact of these functional ingredients on the physico-chemical, microbiological, and sensory properties of yogurt. The milk from same source was equally divided into 9 pails and the 8 ingredients were randomly assigned to the 8 pails. The control had no ingredient. Milk was fermented to yogurt. The pH, titratable acidity, syneresis, viscosity, color (L*, a*, b*, C*, and h*), Streptococcus thermophilus counts, and Lactobacillus delbrueckii spp. bulgaricus counts of yogurts were determined on d 1, 7, 14, 21, 28, 35, and 42, whereas coliform counts, yeast and mold counts, and rheological characteristics were determined on d 1 and 42. The sensory study was performed on d 3 and particle size of the functional ingredients (powder form) was also determined. When compared with control, the incorporation of slippery elm bark into yogurts led to less syneresis. l-Glutamine increased pH and n' values (relaxation exponent derived from G') and lowered titratable acidity values. N-Acetyl-d-glucosamine incorporation resulted in higher n' and lower titratable acidity values, whereas maitake mushroom led to lower n' values. Incorporating quercetin increased the growth of L. bulgaricus. Adding maitake mushrooms increased the growth of S. thermophilus but lowered apparent viscosity values, whereas quercetin decreased its S. thermophilus counts. Quercetin decreased L* and a* values but increased b* values, and maitake mushroom increased a* values. Thixotropic behavior increased with the addition of licorice root and quercetin. Adding slippery elm bark, N-acetyl-d-glucosamine, licorice root, maitake mushrooms, and zinc orotate into yogurt did not affect the sensory properties, whereas yogurts with quercetin had the lowest sensory scores. Overall, most of these ingredients did not cause major changes to yogurt properties.
Metabolic reprogramming in cancer is not only a biological hallmark but also reveals treatment vulnerabilities. Numerous metabolic molecules have shown promise as treatment targets to impede tumor progression in preclinical studies, with some advancing to clinical trials. However, the intricacy and adaptability of metabolic networks hinder the effectiveness of metabolic therapies. This review summarizes the metabolic targets for cancer treatment and provides an overview of the current status of clinical trials targeting cancer metabolism. Additionally, we decipher crucial factors that limit the efficacy of metabolism-based therapies and propose future directions. With advances in integrating multi-omics, single-cell, and spatial technologies, as well as the ability to track metabolic adaptation more precisely and dynamically, clinicians can personalize metabolic therapies for improved cancer treatment.
Fatigue, mood disturbances, lack of performance, and gastrointestinal disturbances are common among athletes during training and competition. Psychosocial and physical demands during intense exercise can initiate a stress response that activates the sympathoadrenal and hypothalamic-pituitary-adrenal axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines, and microbial molecules. The gut is home to trillions of microorganisms that play fundamental roles in many aspects of human biology, including metabolism, neuroendocrine, and immune function. The microbiome and its influence on host behavior, the gut barrier, and immunity is a critical aspect of the gut-brain axis. Data have been obtained showing a high correlation between physical and emotional stress during exercise and changes in the composition of the gastrointestinal microbiota. Modifications to the composition of the microbiota in professional athletes can improve training efficiency, improve athletic performance and shorten the recovery period after intense physical exertion.
Changing Hearts, Changing Minds describes:
1. A multidisciplinary understanding (co-developed with researchers and including social, biological and psychological aspects) of how depression develops in young people – notably the key systems, pathways and mechanisms, and how these offer opportunities for early intervention
2. Specific opportunities for early intervention, including prevention, prediction, detection, diagnosis and treatment
3. How the opportunities can be applied to self-care by individuals and their families, the formal healthcare system and the wider mental health support ecosystem, including schools, mental health support charities, etc.
4. High level suggestions for how the ideas and opportunities can be taken forward to create a better future.
The use of feed additives containing glutamine can influence the growth and development of piglets during the weaning period. The aim of this study was to determine the effect of feed supplementation with 0.5% L-glutamine on selected parameters of the nonspecific immune response of pigs. The research was carried out on 60 pigs (Polish Large White × Polish Landrace), from 28 days of age to slaughter. The obtained results showed an increased percentage of phagocytic cells (monocytes and granulocytes) and oxygen blast cells in pigs between 28 and 70 days of age, proving that non-specific immune mechanisms were stimulated, which contributed to the improvement of the processes of antigen elimination from the body. The increase in the percentage of cells expressing SWC3, CD11b/CD18+, CD14+ and CD14+CD16+ molecules on granulocytes and monocytes during this period resulted in the enhancement of the host defense mechanisms by stimulating phagocytosis and enhancing the mechanisms of a non-specific immune response. The high concentration of TNF-α and IL-1β as well as Il-10 in the experimental group indicates the cellular phenotype of the Th1-type response, and the maintenance of the immune balance between the pro-inflammatory and anti-inflammatory responses and ensuring the homeostasis of the organism.
Consumers are becoming aware of functional ingredients such as medicinal herbs, polyphenols, mushrooms, amino acids, proteins, and probiotics more than ever before. Like yogurt and its probiotics, L-glutamine, quercetin, slippery elm bark, marshmallow root, N-acetyl-D-glucosamine, licorice root, maitake mushrooms, and zinc orotate have demonstrated health benefits through gut microbiota. The impact of these ingredients on yogurt starter culture bacteria characteristics is not well known. The objective of this study was to determine the influence of these ingredients on the probiotic characteristics, tolerance to gastric juices and lysozyme, protease activity, and viability of Streptococcus thermophilus STI-06 and Lactobacillus bulgaricus LB-12. Acid tolerance was determined at 0, 30, 60, 90, and 120 min of incubation, whereas bile tolerance was analyzed at 0, 4, and 8 h. The microbial growth was determined at 0, 2, 4, 6, 8, 10, 12, 14, and 16 h of incubation, while protease activity was evaluated at 0, 12, and 24 h. The application of marshmallow root, licorice root, and slippery elm bark improved bile tolerance and acid tolerance of S. thermophilus. These ingredients did not impact the bile tolerance, acid tolerance, and simulated gastric juice tolerance characteristics of L. bulgaricus over 8 h and 120 min (respectively) of incubation. Similarly, the growth of S. thermophilus and L. bulgaricus was not affected by any of these functional ingredients. The application of marshmallow root, N-acetyl-D-glucosamine, and maitake mushroom significantly increased the protease activity of S. thermophilus, whereas the protease activity of L. bulgaricus was not affected by any ingredient. Compared to the control, marshmallow root and quercetin samples had higher mean log counts and log counts for S. thermophilus on the simulated gastric juice and lysozyme resistance in vitro test, respectively. For L. bulgaricus, licorice root, quercetin, marshmallow root, and slippery elm bark samples had higher log counts than the control samples.
Coccidiosis is acclaimed as the most prevalent enteric parasitic ailment of poultry. It is caused by an apicomplexan protozoon of the genus Eimeria, which resides in chicken intestinal epithelium leading to intestinal damage. As a result, bloody droppings are there, feed efficiency is reduced, the growth rate is impaired, and egg production is temporarily decreased. Treatment and prevention of coccidiosis are primarily accomplished by inoculating live vaccines and administering anticoccidial drugs. Due to anticoccidials’ continuous and excessive use, the mounting issue is drug resistant Eimeria strains. The poultry industry has managed resistance-related issues by suggesting shuttle and rotation schemes. Furthermore, new drugs have also been developed and introduced, but it takes a long time and causes cost inflation in the poultry industry. Moreover, government disallows growth promoters and drugs at sub-therapeutic doses in poultry due to increased concerns about the drug residues in poultry products. These constraints have motivated scientists to work on alternative ways to control coccidiosis effectively, safely, and sustainably. Using nutritional supplements is a novel way to solve the constraints mentioned above. The intriguing aspects of using dietary supplements against coccidiosis are that they reduce the risk of drug-resistant pathogen strains, ensure healthy, nutritious poultry products, have less reliance on synthetic drugs, and are typically considered environmentally safe. Furthermore, they improve productivity, enhance nonspecific immunity, preventing oxidation of fats (acting as antioxidants) and inflammation (acting as an anti-inflammatory). The present manuscript focuses on the efficacy, possible mechanism of action, applications, and different facets of nutrition supplements (such as organic acids, minerals, vitamins, probiotics, essential oils, amino acids, dietary nucleotides, feed enzymes, and yeast derivatives) as feed additive for treating poultry coccidiosis.
Currently, information available on the comprehensive changes in the rumen bacteria and metabolites of yaks fed high-grain diets is limited. This study aimed to investigate the effects of high-grain diet feeding on the blood metabolites, rumen microbiome, and metabolomics of yaks by using 16S rDNA gene sequencing and liquid chromatography–mass spectrometry (LC/MS). Here, fourteen healthy male yaks (body weight, 249.61 ± 8.13 kg) were randomly assigned to two different diets: a hay diet (0% grain, CON, n = 7), or a high-grain diet (70% grain, HG, n = 7). At the 74th day of treatment, blood and ruminal fluid samples were collected for the blood metabolites, rumen microbiome, and metabolomics analyses. The HG diet increased lipopolysaccharides (LPS), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), haptoglobin (HPT), serum amyloid-A (SAA), interleukin-1β (IL1-β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) serum concentrations (p < 0.05). Compared with the CON diet, the HG diet decreased rumen pH (p < 0.05), and increased total volatile fatty acids concentration, and proportion of butyrate (p < 0.05). The relative abundance of Firmicutes and Saccharibacteria were higher (p < 0.05), while Bacteroidetes was lower (p < 0.05) in the HG group than those in the CON group. At the genus level, the relative abundance of Christensenelaceae_R-7_group, Ruminococcaceae_NK4A214_group, Lachnospiraceae_NK3A20_group, and Acetitomaculum were higher than in those in the HG diet (p < 0.05). Compared with the CON group, the HG diet increased the concentrations of biogenic amines (histamine, tyramine, and putrescine), common amino acids (phenylalanine, threonine, serine, etc.), and arachidonic acid (prostaglandin H2, prostaglandin E2, 12(S)-HPETE, etc.). Collectively, these findings demonstrate that the HG diet altered the microbiota and metabolites, as well as potentially damaged their rumen health and induced inflammation in yaks.
The present experiment aimed to research the effects of glutamine (Gln) on the digestive and barrier function of the ruminal epithelium in Hu lambs fed a high-concentrate finishing diet containing some soybean meal and cottonseed meal. Thirty healthy 3-month-old male Hu lambs were randomly divided into three treatments. Lambs were fed a high-concentrate diet and supplemented with 0, 0.5, and 1% Gln on diet for 60 days. The experimental results show that the Gln treatment group had lower pepsin and cellulase enzyme activity, propionate acid concentration, and IL-6, TNF-α, claudin-1, and ZO-1 mRNA expression in the ruminal epithelium (p < 0.05); as well as increases in lipase enzyme activity, the ratio of propionic acid to acetic acid, the IL-10 content in the plasma, and the mRNA expression of IL-2 and IL-10 in the ruminal epithelium, in contrast to the CON (control group) treatment (p < 0.05). Taken together, the findings of this present study support the addition of Gln to improve digestive enzyme activity, the ruminal epithelium’s barrier, and fermentation and immune function by supplying energy to the mononuclear cells, improving the ruminal epithelium’s morphology and integrity, and mediating the mRNA expression of tight junction proteins (TJs) and cytokines.
Epidermal growth factor (EGF) protects the intestinal epithelial tight junctions from acetaldehyde-induced insult. The role of phospholipase Cγ (PLCγ) and protein kinase C (PKC) isoforms in the mechanism of EGF-mediated protection of tight junction from acetaldehyde was evaluated in Caco-2 cell monolayers. EGF-mediated prevention of acetaldehyde-induced decrease in transepithelial electrical resistance and an increase in inulin permeability, and subcellular redistribution of occludin and ZO-1 was attenuated by reduced expression of PLCγ1 by short hairpin RNA. EGF induced a rapid activation of PLCγ1 and PLC-dependent membrane translocation of PKCϵ and PKCβI. Inhibition of PKC activity or selective interference of membrane translocation of PKCϵ and PKCβI by RACK interference peptides attenuated EGF-mediated prevention of acetaldehyde-induced increase in inulin permeability and redistribution of occludin and ZO-1. BAPTA-AM and thapsigargin blocked EGF-induced membrane translocation of PKCβI and attenuated EGF-mediated prevention of acetaldehyde-induced disruption of tight junctions. EGF-induced translocation of PKCϵ and PKCβI was associated with organization of F-actin near the perijunctional region. This study shows that PLCγ-mediated activation of PKCϵ and PKCβI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult.
In this study, we aimed to determine the contribution of substrates to tricarboxylic acid (TCA) cycle fluxes in rumen epithelial cells (REC) and duodenal mucosal cells (DMC) isolated from Angus bulls (n = 6) fed either a 75% forage (HF) or 75% concentrate (HC) diet. In separate incubations, [(13)C(6)]glucose, [(13)C(5)]glutamate, [(13)C(5)]glutamine, [(13)C(6)]leucine, or [(13)C(5)]valine were added in increasing concentrations to basal media containing SCFA and a complete mixture of amino acids. Lactate, pyruvate, and TCA cycle intermediates were analyzed by GC-MS followed by (13)C-mass isotopomer distribution analysis. Glucose metabolism accounted for 10-19% of lactate flux in REC from HF-fed bulls compared with 27-39% in REC from HC and in DMC from bulls fed both diets (P < 0.05). For both cell types, as concentration increased, an increasing proportion (3-63%) of alpha-ketoglutarate flux derived from glutamate, whereas glutamine contributed <3% (P < 0.05). Although leucine and valine were catabolized to their respective keto-acids, these were not further metabolized to TCA cycle intermediates. Glucose, glutamine, leucine, and valine catabolism by ruminant gastrointestinal tract cells has been previously demonstrated, but in this study, their catabolism via the TCA cycle was limited. Further, although glutamate's contribution to TCA cycle fluxes was considerable, it was apparent that other substrates available in the media also contributed to the maintenance of TCA fluxes. Lastly, the results suggest that diet composition alters glucose, glutamate, and leucine catabolism by the TCA cycle of REC and DMC.
There is now evidence that an increased translocation of LPS from gram negative bacteria with subsequent gut-derived inflammation, i.e. induction of systemic inflammation and oxidative & nitrosative stress (IO&NS), is a new pathway in chronic fatigue syndrome (CFS).
The present study examines the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in CFS patients both before and after intake of natural anti-inflammatory and anti-oxidative substances (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet during 10-14 months. We measured the above immune variables as well as the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale in 41 patients with CFS before and 10-14 months after intake of NAIOSs.
Subchronic intake of those NAIOSs significantly attenuates the initially increased IgA and IgM responses to LPS of gram negative bacteria. Up to 24 patients showed a significant clinical improvement or remission 10-14 months after intake of NAIOSs. A good clinical response is significantly predicted by attenuated IgA and IgM responses to LPS, the younger age of the patients, and a shorter duration of illness (< 5 years).
The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in CFS. The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS and that it is a new target for drug development in CFS. Meanwhile, CFS patients with leaky gut can be treated with specific NAIOSs and a leaky gut diet.
During the growth of a tumor, there are very relevant changes in the metabolism of the host to produce the metabolites rapidly consumed by the tumor. In this context, the exchanges of amino acids between the tumor and its host are especially important; however, they have received little attention. A rigorous study must provide data on the growth curve of the tumor, as well as on amino acid levels in tumor cells, plasma, and metabolically relevant tissues and organs from the host during the whole growth of the tumor. The main conclusions arising from a complete study in a tumor model are discussed.
Glutamine (Gln) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this study was to test the hypothesis that Gln regulates intercellular junction integrity and TJ proteins through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Caco-2 cells. Deprivation of exogenous and endogenous glutamine decreased transepithelial electrical resistance (TER) (P < 0.01) and increased permeability (P < 0.01). Both wortmannin and LY294002, PI3K inhibitors, prevented the TER decrease and the permeability increase induced by Gln deprivation (P < 0.001). Gln deprivation also caused decreased TJ protein claudin-1 (P < 0.001). Both wortmannin and LY294002 treatment prevented this effect (P < 0.001). Deprivation of Gln increased phosphor-Akt protein. Gln supplementation reversed this effect. Decreased TER and increased permeability associated with Gln deprivation were not observed in small interfering RNA for p85 transfected Caco-2 cells. In conclusion, Gln regulates intercellular junction integrity and TJ proteins through the PI3-Kinase/Akt pathway.
Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.
This study was performed to determine whether the addition of alanyl-glutamine (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing 250 g were randomly divided into four groups: group I was killed after overnight fasting; group II received S-TPN. The other groups received S-TPN supplemented with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2 g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1 week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small bowel, and distal ileum were obtained for morphologic and functional analysis. Weight gain did not differ significantly among these four groups, and there was no difference in nitrogen balance between groups III and IV. Serum glutamine in group IV (102.8 +/- 13.3 mumol/dL) was significantly increased (p less than .05) compared with groups I, II, and III (66.2 +/- 3.9, 55.7 +/- 7.8, and 61.3 +/- 10.8 mumol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and maltase of group IV were significantly increased (p less than .05) compared with groups II and III. Villus height was significantly increased (p less than .05) in the jejunum of group IV rats compared with groups II and III, but not in any other segments of the intestine. No significant changes were observed in crypt depth among all groups. Diamine oxidase in groups II, III, and IV was significantly decreased (p less than .05) compared with group I in all segments except for the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.