Hold the Door: Role of the Gut Barrier in Diabetes

Martin, Anthony; Devkota, Suzanne

doi:10.1016/j.cmet.2018.04.017

Cited by 13 publications

(12 citation statements)

References 8 publications

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“…1 Breakdown of the intestinal barrier is a hallmark of inflammatory bowel disease 2 and celiac disease, 3 and is thought to lead to translocation of gut microbiota, noxious molecules, and systemic immune dysregulation. 1 Recent studies suggest that there is increased intestinal permeability in several metabolic, 4 infectious, 5 and autoimmune conditions, 6 but the clinical or pathogenic significance of these findings has not always been clear.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

et al. 2019

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Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured. Results: Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood–brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad– subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS. Conclusions: People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut–brain axis modulates neuroinflammation in MS.

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Section: Introductionmentioning

confidence: 99%

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

et al. 2019

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“…The weakening of intercellular junctions between intestinal epithelial cells will result in increased intestinal permeability and systemic exposure to bacterial antigens. The increased diffusion of bacterial components into the blood, lymph, and other extraintestinal tissues is closely related with critical illness, inflammatory bowel disease, celiac disease, food allergy, irritable bowel syndrome, and metabolic syndromes such as diabetes and obesity [2][3][4]. Therefore, intestinal epithelial permeability provides a novel target for disease prevention and therapy [5,6].…”

Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells: Regulators of Gut Barrier Function and Immune Homeostasis

Fan

Wang

et al. 2019

Journal of Immunology Research

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Innate lymphoid cells (ILCs), identified in the early years of this century as a new class of leukocyte family unlike the B or T lymphocytes, play a unique role bridging the innate and adaptive immune responses in mucosal immunity. Their origin, differentiation, and activation process and functions have caught global interest. Recently, accumulating evidence supports that ILCs are vital regulators for gastrointestinal mucosal homeostasis through interactions with other structural and stromal cells in gut epithelial barriers. This review will explore the functions of ILCs and other cells in maintaining gut homeostasis and feature the crosstalk between ILCs with other cells and potential pharmacotherapy targeting ILCs applicable in intestinal innate immunity.

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“…Numerous studies have established the role of metabolic endotoxemia in the development of type 2 diabetes (T2D) [ 6 ], and the gut barrier integrity appeared to be disturbed in diabetic condition [ 31 , 32 ]. To elucidate the protective role of andrographolide against T2D, we performed the glucose tolerance test (GTT) and insulin tolerance test (ITT) in db/db mice orally treated with andrographolide (150 mg/kg per mice) or vehicle for 8 weeks.…”

Section: Resultsmentioning

confidence: 99%

Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila

et al. 2020

Oxidative Medicine and Cellular Longevity

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Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.

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Hold the Door: Role of the Gut Barrier in Diabetes

Cited by 13 publications

References 8 publications

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

Innate Lymphoid Cells: Regulators of Gut Barrier Function and Immune Homeostasis

Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila

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