Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice
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Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice. / Hansen, Camilla H. F.; Larsen, Christian S.; Petersson, Henriette O.; Zachariassen, Line F.; Vegge, Andreas; Lauridsen, Charlotte; Kot, Witold; Krych, Lukasz; Nielsen, Dennis S.; Hansen, Axel K.
In: Diabetologia, Vol. 62, No. 9, 2019, p. 1689-1700.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice
AU - Hansen, Camilla H. F.
AU - Larsen, Christian S.
AU - Petersson, Henriette O.
AU - Zachariassen, Line F.
AU - Vegge, Andreas
AU - Lauridsen, Charlotte
AU - Kot, Witold
AU - Krych, Lukasz
AU - Nielsen, Dennis S.
AU - Hansen, Axel K.
PY - 2019
Y1 - 2019
N2 - Aims/hypothesisAdopting 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.MethodsMother 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.ResultsDiabetes 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/interpretationPrebiotic XOS have microbiota-dependent effects on salivary gland inflammation and microbiota-independent 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.
AB - Aims/hypothesisAdopting 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.MethodsMother 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.ResultsDiabetes 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/interpretationPrebiotic XOS have microbiota-dependent effects on salivary gland inflammation and microbiota-independent 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.
KW - Gut barrier
KW - Gut microbiota
KW - Insulitis
KW - Mucosal immunology
KW - Prebiotics
KW - Sialadenitis
KW - XOS
U2 - 10.1007/s00125-019-4910-5
DO - 10.1007/s00125-019-4910-5
M3 - Journal article
C2 - 31139852
VL - 62
SP - 1689
EP - 1700
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 9
ER -
ID: 225956324