scholarly journals Role for diet in normal gut barrier function: developing guidance within the framework of food-labeling regulations

2019 ◽  
Vol 317 (1) ◽  
pp. G17-G39 ◽  
Author(s):  
Michael Camilleri ◽  
Barbara J. Lyle ◽  
Karen L. Madsen ◽  
Justin Sonnenburg ◽  
Kristin Verbeke ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Normal Function ◽  
Model Systems ◽  
Intestinal Barrier Function ◽  
Dietary Interventions ◽  
Labeling Regulations ◽  
Gut Barrier Function ◽  
And Function

A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharide, peptidoglycan, whole bacteria, and other toxins to traverse the barrier to damage the intestine or enter the portal circulation. Currently available evidence in animal models and in vitro systems has shown that certain dietary interventions can be used to reinforce the intestinal barrier to prevent the development of disease. The relevance of these studies to human health is unknown. Herein, we define the components of the intestinal barrier, review available modalities to assess its structure and function in humans, and review the available evidence in model systems or perturbations in humans that diet can be used to fortify intestinal barrier function. Acknowledging the technical challenges and the present gaps in knowledge, we provide a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease. Such evidence would provide information on the development of healthier diets and serve to provide a framework by which federal agencies such as the US Food and Drug Administration can evaluate evidence linking diet with normal human structure/function claims focused on reducing risk of disease in the general public.

The Effects of Sulfated Secondary Bile Acids on Intestinal Barrier Function and Immune Response in an Inflammatory in vitro Human Intestinal Model

2021 ◽  
Author(s):  
Benthe van der Lugt ◽  
Maartje C.P. Vos ◽  
Mechteld Grootte Bromhaar ◽  
Noortje Ijssennagger ◽  
Frank Vrieling ◽  
...  
Keyword(s):  
Immune Response ◽  
Bile Acids ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Secondary Bile Acids

scholarly journals Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 102-108 ◽  
Author(s):  
Norio Nishii ◽  
Tadayuki Oshima ◽  
Min Li ◽  
Hirotsugu Eda ◽  
Kumiko Nakamura ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Fluorescein Isothiocyanate ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Epithelial Permeability ◽  
Epithelial Barrier Function ◽  
Dose Dependent

Introduction: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. Methods: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. Results: IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. Conclusion: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

scholarly journals 2’-fucosyllactose (2’-FL) Supplementation Improves Gut Barrier Function and Lipid Metabolism in HF-fed Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 425-425
Author(s):  
Sunhye Lee ◽  
Michael Goodson ◽  
Wendie Vang ◽  
Karen Kalanetra ◽  
Daniela Barile ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Barrier ◽  
Low Fat ◽  
Barrier Integrity ◽  
Gut Barrier Function

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).

scholarly journals Gut barrier function in malnourished patients

Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 396-401 ◽  
Author(s):  
F K S Welsh ◽  
S M Farmery ◽  
K MacLennan ◽  
M B Sheridan ◽  
G R Barclay ◽  
...  
Keyword(s):  
Acute Phase ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Molecular Evidence ◽  
Gut Barrier ◽  
Gut Barrier Function ◽  
Hospitalised Patients ◽  
Increased Risk

Background—The integrity of the gastrointestinal mucosa is a key element in preventing systemic absorption of enteric toxins and bacteria. In the critically ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients have an increased risk of postoperative sepsis; however, the effects of malnutrition on intestinal barrier function in man are unknown.Aims—To quantify intestinal barrier function, endotoxin exposure, and the acute phase cytokine response in malnourished patients.Patients—Malnourished and well nourished hospitalised patients.Methods—Gastrointestinal permeability was measured in malnourished patients and well nourished controls using the lactulose:mannitol test. Endoscopic biopsy specimens were stained and morphological and immunohistochemical features graded. The polymerase chain reaction was used to determine mucosal cytokine expression. The immunoglobulin G antibody response to endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent assay.Results—There was a significant increase in intestinal permeability in the malnourished patients in association with phenotypic and molecular evidence of activation of lamina propria mononuclear cells and enterocytes, and a heightened acute phase response.Conclusions—Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear.

scholarly journals Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

2020 ◽  
Author(s):  
Jingtao Wu ◽  
Caimei He ◽  
Jie Bu ◽  
Yue Luo ◽  
Shuyuan Yang ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Vital Role ◽  
Inflammatory Factors ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Epithelial Barriers ◽  
Vitro Model

Abstract Background：The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model. Results: The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1µg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription- polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

scholarly journals Engineered Butyrate-producing Bacillus Subtilis Alleviated Ethanol-induced Intestinal and Liver Damage in Mice

2020 ◽  
Author(s):  
Xing Lu ◽  
Meiqi Zhao ◽  
Yitao Duan ◽  
Fengmei Wang ◽  
Chuanai Chen
Keyword(s):  
Bacillus Subtilis ◽  
Barrier Function ◽  
Circulatory System ◽  
Intestinal Barrier ◽  
Ethanol Exposure ◽  
Intestinal Barrier Function ◽  
Intestinal Dysbiosis ◽  
Ethanol Feeding ◽  
And Function ◽  
Binge Ethanol

Abstract Ethanol-induced intestinal and liver injury are closely associated with intestinal dysbiosis and altered short-chain fatty acid (SCFA) metabolites which is crucial for intestinal health. Bacillus subtilis (BS) strains with biotherapeutic potential can benefit the host through maintaining intestinal homeostasis and regulating systematic immunity via producing small molecules, although these molecules do not include butyrate. To combine the advantages of butyrate and BS, we evaluated the bioactivity of an engineered butyrate-producing Bacillus subtilis (BPBS) strain against ethanol exposure in a chronic-binge ethanol feeding mouse model. Our findings suggested that prophylactic BPBS supplementation restored eubiosis of the gut microbiota and intestinal barrier function, which obviously reduced bacterial translocation of microbial products especially lipopolysaccharide (LPS) to the circulatory system. Additionally, the decrease of serum LPS is responsible for the relief of hepatic inflammation via the Toll-like receptor 4 (TLR4) pathway, resulting in improved hepatic structure and function. Collectively, these results demonstrated that engineered BPBS intervention imparted novel hepatoprotective functions by improving intestinal barrier function and reducing systematic inflammation under ethanol exposure, as well as paving the way for further exploration of engineered probiotics in improving human health care.

scholarly journals Bile salt dependent lipase promotes intestinal adaptation in rats with massive small bowel resection

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Yi Yang ◽  
Tao Zheng ◽  
Jiefei Zhou ◽  
Huanlei Song ◽  
Wei Cai ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Bile Salt ◽  
Barrier Function ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Intestinal Barrier ◽  
Untreated Group ◽  
Intestinal Barrier Function ◽  
Adaptive Growth ◽  
Gut Barrier Function

Intestinal adaptation is important for the short bowel syndrome (SBS) patients. Growing evidence has suggested that bile salt dependent lipase (BSDL) not only has the lipolytic activity, but also the immune-modulating and pro-proliferative activities. The purpose of the present study was to investigate the effects of BSDL on intestinal adaptive growth and gut barrier function in a rat model of SBS. Twenty-four male Sprague–Dawley rats were randomly divided into three experimental groups: sham group (rats underwent bowel transection and re-anastomosis), SBS group (rats underwent 80% bowel resection), SBS-BSDL group (SBS rats orally administered BSDL). The animals were weighed daily. The intestinal morpho-histochemical changes and intestinal barrier function were determined 14 days after the operations. Meanwhile, the expressions of Wnt signaling molecules in enterocytes were also analyzed by immunohistochemistry and Western blot. The postoperative weight gain was faster in the SBS rats treated with BSDL than in the SBS/untreated group. The SBS rats treated with BSDL had significantly greater villus height, crypt depth, and enterocyte proliferation in their residual intestines, as compared with the SBS/untreated group. The recovery of intestinal barrier function was promoted and the expressions of tight-junction proteins were increased in the SBS rats treated with BSDL. Additionally, the data indicated that the proadaptive activities of BSDL might be mediated by Wnt signaling activation in the enterocytes. These observations suggested that enteral BSDL administration promoted intestinal adaptive growth and barrier repairing by activating Wnt signaling pathway in SBS rats.

scholarly journals Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Magdalena Kasendra ◽  
Raymond Luc ◽  
Jianyi Yin ◽  
Dimitris V Manatakis ◽  
Gauri Kulkarni ◽  
...  
Keyword(s):  
Drug Transport ◽  
Intestinal Barrier ◽  
New Drugs ◽  
Intestinal Barrier Function ◽  
Human Pharmacokinetics ◽  
Relevant Model ◽  
Cell Subpopulations ◽  
And Function

Induction of intestinal drug metabolizing enzymes can complicate the development of new drugs, owing to the potential to cause drug-drug interactions (DDIs) leading to changes in pharmacokinetics, safety and efficacy. The development of a human-relevant model of the adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids and Organs-on-Chips technology to create a human Duodenum Intestine-Chip that emulates intestinal tissue architecture and functions, that are relevant for the study of drug transport, metabolism, and DDI. Duodenum Intestine-Chip demonstrates the polarized cell architecture, intestinal barrier function, presence of specialized cell subpopulations, and in vivo relevant expression, localization, and function of major intestinal drug transporters. Notably, in comparison to Caco-2, it displays improved CYP3A4 expression and induction capability. This model could enable improved in vitro to in vivo extrapolation for better predictions of human pharmacokinetics and risk of DDIs.

Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route

2017 ◽  
Vol 313 (6) ◽  
pp. G537-G548 ◽  
Author(s):  
Silke S. Zakrzewski ◽  
Michael Fromm ◽  
Jörg D. Schulzke ◽  
Dorothee Günzel
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Secretory Diarrhea ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Gastrointestinal Infections ◽  
Apical Side

During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. To analyze the molecular mechanism whereby Zn acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools. Feeding pharmacological Zn doses exerted no significant electrophysiologically ascertainable short- and long-term effects on jejunal barrier function ex vivo. However, in IPEC-J2/PS, basolateral Zn was cytotoxic since its application caused a release of lactate dehydrogenase and an irreversible breakdown of the epithelial barrier. In contrast, apical Zn application caused an immediate increase in paracellular resistance and a decrease in permeability to the paracellular marker fluorescein, reflecting overall barrier strengthening in vitro. Apical effects were fully reversible upon washout. This indicates that Zn supplemented to feed was completely washed out during ex vivo jejunum preparation. We conclude that there is no evidence for long-term barrier effects through prophylactic Zn supplementation and that extracellular Zn acts acutely and reversibly from the apical side via tightening the paracellular route, thus counteracting leak-flux diarrhea. NEW & NOTEWORTHY Therapeutically administered Zn successfully treats diarrhea in veterinary and human medicine. Here we present data that Zn strengthens the porcine jejunal epithelial barrier by reversibly tightening the paracellular route for inorganic ions and small solutes. Acute or long-lasting Zn effects on transcellular transport (Cl− secretion) were not detected. We therefore conclude that Zn is useful for acutely treating leak-flux diarrhea rather than secretory diarrhea. Suitability as prophylactic feed supplement, however, is questionable.

Sign in / Sign up

Export Citation Format

Share Document