Gut barrier integrity is indispensable for health and has been recognized as a key mechanism through which probiotics exert their beneficial effects. Recently, Alistipes indistinctus (A. indistinctus) has attracted increasing interest due to its pleiotropic benefits on metabolic homeostasis. However, evidence supporting its probiotic properties remains limited. Here, genomic analysis followed by a series of in vitro and in vivo studies was performed to systematically evaluate the safety, gastrointestinal tolerance, adhesive capacity, and intestinal barrier protection effect of A. indistinctus. A. indistinctus exhibited a high genomic sequence similarity with Bifidobacterium spp., an established probiotic, and encoded a variety of genes related to antioxidation and bile salt hydrolysis. The survival rate of A. indistinctus in gastric and intestinal fluid was 77.3% and 73.0%, respectively, comparable to most well-known probiotics. Transmission electron microscopy analysis further demonstrated that only live A. indistinctus exhibited a high adherence capacity to intestinal villi, which facilitated its colonization. Consistently, oral administration of live A. indistinctus led to a 1.5-fold increase in the number of goblet cells, which in turn boosted the formation and thickness of mucus layer in germ-free mice, and enhanced the expression of tight junctions, with no sign of liver and renal injury. Similarly, co-culture with A. indistinctus substantially reversed the impaired expression of mucin 2 in LS174T and zonula occludens-1 and occludin in Caco-2 cells, induced by lipopolysaccharide exposure. Mechanistically, A. indistinctus enhanced gut integrity and protected against lipopolysaccharide-induced inflammation by suppressing the nuclear translocation and activation of nuclear factor kappa-B p65 in both goblet and epithelial cells. Collectively, our findings provide a mechanistic basis for the protective effects of A. indistinctus on intestinal barrier integrity, highlighting its potential as a next-generation probiotic.
Xu et al. (Sun,) studied this question.