PT  - JOURNAL ARTICLE
AU  - Radhika Gudi
AU  - Nicolas Perez
AU  - Benjamin M. Johnson
AU  - M.Hanief Sofi
AU  - Robert Brown
AU  - Songhua Quan
AU  - Subha Karumuthil-Melethil
AU  - Chenthamarakshan Vasu
TI  - Complex dietary-polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes
AID  - 10.1101/492637
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 492637
4099  - http://biorxiv.org/content/early/2018/12/10/492637.short
4100  - http://biorxiv.org/content/early/2018/12/10/492637.full
AB  - Since the dietary supplement and prebiotic value of β-glucan-rich products have been widely recognized and the dietary approaches for modulating autoimmunity have been increasingly explored, we assessed the impact of oral administration of high-pure yeast β-glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a Dectin-1-dependent immune response involving increased expression of IL10, retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa. YBG-exposed intestinal DCs induced/expanded primarily Foxp3+, IL10+ and IL17+ T cells, ex vivo. Importantly, prolonged oral administration of low-dose YBG at pre-diabetic stage suppressed insulitis and significantly delayed the T1D incidence in non-obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3+ T cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh-substrate and β-cell antigen, resulted in a better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also has an oral tolerogenic-adjuvant-like effect, and these features could be exploited for modulating autoimmunity in T1D.