Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice

Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease. The review shows that many factors such as the mode of delivery, breast milk, stress, diet and medications can greatly influence the development of our gut microbiome and potentially make us more prone to certain diseases. By incorporating environmental factors into models that study the microbiome in the setting of health and disease, may provide a better understanding of disease and potentially new areas of treatment. To highlight this, we will additionally explore the role of the environment and the microbiome in the development of obesity and functional bowel disorders.

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“…31 In a mouse model, human milk oligosaccharides were found to be protective in the development of autoimmune disease and obesity. 32,33 …”

Section: Environmental Factorsmentioning

confidence: 99%

Influence of Early Life, Diet, and the Environment on the Microbiome

Dong

Gupta

2019

Clinical Gastroenterology and Hepatology

158

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“…Besides modulating the composition of the gut microbiota, dietary fibre is fermentable in the large intestine and forms an important source of shortchain fatty acids (SCFA) with a nutritional role for the epithelial cells lining the gut barrier [12]. Some polysaccharides, such as pectin and xylan, are associated with higher levels of proinflammatory and stress-related transcripts in the colon and have diabetogenic potential in NOD mice [12], whereas human milk oligosaccharides, for example, have a tolerogenic effect on the immune system and reduce diabetes incidence in NOD mice [13]. Toivonen et al [12] explain that differences in fibre digestion result in different effects on the microbiota and variation in outcome for the host.…”

Section: Introductionmentioning

confidence: 99%

Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice

et al. 2019

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Aims/hypothesis Adopting a diet containing indigestible fibre compounds such as prebiotics to fuel advantageous bacteria has proven beneficial for alleviating inflammation. The effect of the microbial changes on autoimmunity, however, remains unknown. We studied the effects of prebiotic xylooligosaccharides (XOS) on pancreatic islet and salivary gland inflammation in NOD mice and tested whether these were mediated by the gut microbiota. Methods Mother and offspring mice were fed an XOS-supplemented diet until diabetes onset or weaning and were compared with a control-fed group. Diabetes incidence was monitored, insulitis and sialadenitis were scored in histological sections from adult mice, and several metabolic and immune variables were analysed in mice before the development of diabetes. Gut barrier function was assessed using an in vivo FITC-dextran permeability test. The importance of XOS-mediated gut microbial changes were evaluated in antibiotic-treated mice fed either XOS or control diet or given a faecal microbiota transplant from test animals. Results Diabetes onset was delayed in the XOS-fed mice, which also had fewer cellular infiltrations in their pancreatic islets and salivary glands. Interestingly, insulitis was most reduced in the XOS-fed groups when the mice were also treated with an antibiotic cocktail. There was no difference in sialadenitis between the dietary groups treated with antibiotics; the mice were protected by microbiota depletion regardless of diet. Faecal microbiota transplantation was not able to transfer protection. No major differences in glucose-insulin regulation, glucagon-like peptide-1, or short-chain fatty acid production were related to the XOS diet. The XOS diet did, however, reduce gut permeability markers in the small and large intestine. This was accompanied by a more anti-inflammatory environment locally and systemically, dominated by a shift from M1 to M2 macrophages, a higher abundance of activated regulatory T cells, and lower levels of induction of natural killer T cells and cytotoxic T cells. Conclusions/interpretation Prebiotic XOS have microbiota-dependent effects on salivary gland inflammation and microbiotaindependent effects on pancreatic islet pathology that are accompanied by an improved gut barrier that seems able to heighten control of intestinal diabetogenic antigens that have the potential to penetrate the mucosa to activate autoreactive immune responses.

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“…90 These protective effects were associated with a preferential increase of the SCFA-producing bacteria Lachnospiraceae, accompanied by higher serum levels of antidiabetogenic cytokines. 90 Caseins are proteins commonly found in mammalian milk, accounting for up to 45% of the proteins in human milk. 134 An interventional study involving 230 Finnish infants at risk of T1D noted a 50% reduction in the incidence of islet autoimmunity upon weaning from diets enriched with hydrolyzed casein compared with traditional cow's milk-based formula.…”

Section: Probiotics and Prebioticsmentioning

confidence: 99%

“…Moreover, a reduction in SCFA‐producing bacteria was noted in T1D at the time of onset of autoimmunity, which was associated with impaired gut barrier functions . Dietary intake of 1% authentic HMOs during early life for a period of 6 weeks delayed T1D development in NOD mice . These protective effects were associated with a preferential increase of the SCFA‐producing bacteria Lachnospiraceae, accompanied by higher serum levels of antidiabetogenic cytokines .…”

Section: Modulation Of Gut Microbiome For Treatment Of T1dmentioning

confidence: 99%

“…Dietary intake of 1% authentic HMOs during early life for a period of 6 weeks delayed T1D development in NOD mice . These protective effects were associated with a preferential increase of the SCFA‐producing bacteria Lachnospiraceae, accompanied by higher serum levels of antidiabetogenic cytokines . Caseins are proteins commonly found in mammalian milk, accounting for up to 45% of the proteins in human milk .…”

Section: Modulation Of Gut Microbiome For Treatment Of T1dmentioning

confidence: 99%

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Current understanding of the role of gut dysbiosis in type 1 diabetes

Abdellatif

Sarvetnick

2019

Journal of Diabetes

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Type 1 diabetes (T1D) is a chronic autoimmune disorder that results from destruction of the insulin‐producing pancreatic β‐cells. The disease mainly affects juveniles. Changes in the composition of the gut microbiota (dysbiosis) and changes in the properties of the gut barrier have been documented in T1D subjects. Because these factors affect immune system functions, they are likely to play a role in disease pathogenesis. However, their exact role is currently not fully understood and is under intensive investigation. In this article we discuss recent advancements depicting the role of intestinal dysbiosis on immunity and autoimmunity in T1D. We also discuss therapies aimed at maintaining a healthy gut barrier as prevention strategies for T1D.

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Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice

Cited by 82 publications

References 60 publications

Influence of Early Life, Diet, and the Environment on the Microbiome

Influence of Early Life, Diet, and the Environment on the Microbiome

Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice

Current understanding of the role of gut dysbiosis in type 1 diabetes

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