Homeostasis of the gut barrier and potential biomarkers

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.

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Loss of Maternal microRNA Miogenesis Impairs Gut Health in Wild-Type Pups Fostered to Dicer Knockout Dams

Current Developments in Nutrition ◽

10.1093/cdn/nzaa054_185 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1113-1113

Author(s):

Fang Zhou ◽

Janos Zempleni

Keyword(s):

Barrier Function ◽

Cell Communication ◽

Gut Health ◽

Wild Type ◽

Gut Barrier ◽

Microrna Biogenesis ◽

Funding Sources ◽

Gut Barrier Function ◽

Gates Foundation ◽

Quality Of Milk

Abstract Objectives Exosomes play a role in cell-to-cell communication, which is achieved by the transfer of microRNAs from donor cells to recipient cells. Exosomes and their microRNA cargos may also be absorbed from milk and accumulate primarily in the intestinal mucosa, kidneys and brains in C57BL/6 pups. MicroRNA biogenesis depends on the endonuclease Dicer, and homozygous Dicer KO is lethal. We hypothesized maternal microRNA biogenesis would be important for optimal postnatal development of pups. This study aimed to assess whether maternal loss of microRNA biogenesis impairs the nutritional quality of milk and gut health in wild-type (WT) pups fostered to Dicer knockout (KO) dams. Methods WT C57BL/6 pups were fostered to tamoxifen-inducible heterozygous Dicer KO dams from synchronized pregnancies (4 pups/dam). In the treatment group, one allele of Dicer was knockout out in dams by i.p. tamoxifen injection after delivery (denoted “Dicer KO”); control dams were injected with vehicle (denoted “CTRL”). Milk was collected 11 days postpartum for analysis of exosomal microRNAs (RT-qPCR), lactose (enzymatic), total protein (BCA assay), total triglycerides (Vitros 250 Analyzer) and water (weighing oven). Postnatal gut morphology and gut barrier function were assessed by histology analysis and oral FITC-dextran at age 3 weeks. The unpaired t-test was used for statistical analysis; P < 0.05 was considered statistically significant. Results The expression of microRNAs in exosomes decreased by 60% in Dicer KO dams compared to CTRL. The loss of maternal microRNA biogenesis impaired gut health in WT pups: 1) The length of the gastrointestinal tract and the width of jejunum decreased by more than 33% and 41% in WT pups fostered to Dicer KO dams, respectively, compared to pups fostered to CTRL. 2) The villi height decreased by 20% (female) and 10% (male) in WT pups fostered Dicer KO dams compared to pups fostered to CTRL. 3) Gut barrier function was impaired, as evidenced by a peak FITC-dextran plasma concentration that was 59% higher in pups fostered to Dicer KO compared to CTRL after oral FITC-dextran. Dicer KO had no effect on the content of macronutrients and water in milk. Conclusions MicroRNAs in milk play a role in optimal postnatal gut health during lactation. Funding Sources NIFA, NIH, Gates Foundation and USDA. J.Z. is a consultant for PureTech Health.

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Food Allergies and Ageing

International Journal of Molecular Sciences ◽

10.3390/ijms20225580 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5580 ◽

Cited By ~ 8

Author(s):

Massimo De Martinis ◽

Maria Maddalena Sirufo ◽

Angelo Viscido ◽

Lia Ginaldi

Keyword(s):

Barrier Function ◽

The Elderly ◽

Food Allergies ◽

Secretory Iga ◽

Regulatory Function ◽

Gut Barrier ◽

Th2 Response ◽

Gut Barrier Function ◽

Inflammatory Status

All over the world, there is an increase in the overall survival of the population and the number of elderly people. The incidence of allergic reactions is also rising worldwide. Until recently, allergies, and in particular food allergies (FAs), was regarded as a pediatric problem, since some of them start in early childhood and may spontaneously disappear in adulthood. It is being discovered that, on the contrary, these problems are increasingly affecting even the elderly. Along with other diseases that are considered characteristics of advanced age, such as cardiovascular, dysmetabolic, autoimmune, neurodegenerative, and oncological diseases, even FAs are increasingly frequent in the elderly. An FA is a pleiomorphic and multifactorial disease, characterized by an abnormal immune response and an impaired gut barrier function. The elderly exhibit distinct FA phenotypes, and diagnosis is difficult due to frequent co-morbidities and uncertainty in the interpretation of in vitro and in vivo tests. Several factors render the elderly susceptible to FAs, including the physiological changes of aging, a decline in gut barrier function, the skewing of adaptive immunity to a Th2 response, dysregulation of innate immune cells, and age-related changes of gut microbiota. Aging is accompanied by a progressive remodeling of immune system functions, leading to an increased pro-inflammatory status where type 1 cytokines are quantitatively dominant. However, serum Immunoglobulin E (IgE) levels and T helper type 2 (Th2 cytokine production have also been found to be increased in the elderly, suggesting that the type 2 cytokine pattern is not necessarily defective in older age. Dysfunctional dendritic cells in the gut, defects in secretory IgA, and decreased T regulatory function in the elderly also play important roles in FA development. We address herein the main immunologic aspects of aging according to the presence of FAs.

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Centenarian-Sourced Lactobacillus casei Combined with Dietary Fiber Complex Ameliorates Brain and Gut Function in Aged Mice

Nutrients ◽

10.3390/nu14020324 ◽

2022 ◽

Vol 14 (2) ◽

pp. 324

Author(s):

Minhong Ren ◽

He Li ◽

Zhen Fu ◽

Quanyang Li

Keyword(s):

Dietary Fiber ◽

Barrier Function ◽

Lactobacillus Casei ◽

Dietary Intervention ◽

Short Chain Fatty Acids ◽

Gut Barrier ◽

Aged Mice ◽

Gut Barrier Function ◽

Age Related ◽

Gut Function

Dietary intervention could modulate age-related neurological disorders via the gut–brain axis. The potential roles of a probiotic and the dietary fiber complex (DFC) on brain and gut function in aged mice were investigated in this study. Lactobacillus casei LTL1361 and DFC were orally administrated for 12 weeks, and the learning and memory ability, as well as the oxidative parameters, inflammatory markers, gut barrier function and microbial metabolite short-chain fatty acids (SCFAs), were investigated. LTL1361 and DFC supplementation ameliorated cognitive ability, attenuated oxidative stress in brain and inflammation in serum and colon, ameliorated gut barrier function, and increased the SCFA concentrations and gene expression of SCFA receptors. The protective effect was more significantly enhanced in aged mice treated with the combination of LTL1361 and DFC than treated with LTL1361 or DFC alone. These results could be associated with the protected morphology of pyramidal nerve cells in hippocampus of mice brain and the downregulation of apoptosis marker caspase-3 in brain and upregulation of tight junction proteins in small intestine and colon. The results indicated that Lactobacillus casei LTL1361 and DFC alleviated age-related cognitive impairment, as well as protected brain and gut function. Lactobacillus casei LTL1361 and DFC might be used as novel and promising antiaging agents in human.

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