Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Abstract

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.

Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis

“…Although Crohn’s disease was initially characterized as a Th1- and UC as a Th2-driven inflammatory disease, additional T cell subsets have been identified to play a role in IBD mucosal barrier immunity including regulatory T cells and IL-23 responsive Th17 cells (15). In mouse models, human microbiota have been shown to play a critical role in regulating Th1 (19), regulatory T cells (20), and Th17 (16, 21). Immune cell analyses in FMT studies have been limited, but a recent analysis in Crohn’s disease revealed a borderline increase in CD25+ CD127 lo CD4+ T cells at 12 weeks post-FMT (17).…”

Microbiota and reproducibility of rodent models

“…These now include protozoans such as Tritrichomonas spp 67, 68 . and a human isolate of Bifidobacterium adolescentis 69 . While single agents are being implicated, it is also highly likely that more complex communities of multiple agents will likely have equally important, if not more important, roles in model phenotypes 70 .…”

Gut Microbiota: What We Could Do, Not Just Use ‘Young Healthy Poo’ for Drugs?

“…For example, Th17 cells accumulate in the gut and take its role as the safeguards there by secreting cytokines like IL-17 and IL-22, and inducing some antimicrobial peptides and tight junction proteins from intestinal epithelial cells [17][18][19]. Both segmented filamentous bacteria (SFB) from mice's gut [20][21][22] and B. adolescentis from human' [23] could induce T Helper 17 cells (Th17). Not surprisingly, gut microbiota-derived products, such as short-chain fatty acids (SCFAs), adenosine triphosphate (ATP) and various cytokines could also regulate the immune cells and immune response directly or indirectly [23].…”

“…Both segmented filamentous bacteria (SFB) from mice's gut [20][21][22] and B. adolescentis from human' [23] could induce T Helper 17 cells (Th17). Not surprisingly, gut microbiota-derived products, such as short-chain fatty acids (SCFAs), adenosine triphosphate (ATP) and various cytokines could also regulate the immune cells and immune response directly or indirectly [23]. For instance, excessive production and accumulation of SCFAs such as acetic acid, propionic acid and butyric acid, cause the increased luminal carbohydrates malabsorption and poor gastrointestinal motility, and ultimately might lead to the necrotizing enterocolitis, especially premature infants, whose immune systems are not fully established.…”

“…Various immune cells are involved in this process and most of them have receptors for SCFAs, but which is particularly responsible for this is poorly discussed. On the other hand, IgA is the crucial host immune effector to modulate microbiota back [23]. However, we know much less about how certain immune cells control or regulate gut microbiota, by phagorytosis or by secreted cytokines or something else?…”