Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations in social, repetitive, and anxiety-like behaviors. While emerging evidence suggest a gut-brain etiology in ASD, the underlying mechanisms remain unclear. To dissect this axis, we developed a germ-free BTBR mouse model for ASD. The absence of gut microbiota in male mice ameliorates ASD-associated behaviors and reduces populations of inflammatory brain-resident T cells. Additionally, CD4⁺ T cell depletion mitigates neuroinflammation and ASD behaviors, suggesting a gut-immune-brain axis. We identify several microbial and metabolic regulators of ASD, particularly those relevant to the glutamate/GABA ratio and 3-hydroxyglutaric acid. Using an in silico metabolite prediction model, we propose Limosilactobacillus reuteri IMB015 (IMB015) to be a probiotic candidate. Administration of IMB015 reduces the glutamate/GABA ratio and neuroinflammation, resulting in improved behaviors. Here we report a gut-immune-brain axis in which the gut microbiota and its metabolites can modulate brain-resident immune cells and ASD-associated behaviors.

The gut microbiota plays an essential role in mucosal immunity, with secretory immunoglobulin A (IgA) acting as a key effector in neutralizing pathogens an

The composition and diversity of gut microbiota significantly influence the immune system and are linked to various diseases, including inflammatory and allergy disorders. While considerable research has focused on exploring single bacterial species or consortia, the optimal strategies for microbiota-based therapeutics remain underexplored. Specifically, the comparative effectiveness of bacterial consortia versus individual species warrants further investigation. In our study, we assessed the impact of the bacterial consortium MPRO, comprising Lactiplantibacillus plantarum HY7712, Bifidobacterium animalis ssp. lactis HY8002, and Lacticaseibacillus casei HY2782, in comparison to its individual components. The administration of MPRO demonstrated enhanced therapeutic efficacy in experimental models of atopic dermatitis and inflammatory colitis when compared to single strains. MPRO exhibited the ability to dampen inflammatory responses and alter the gut microbial landscape significantly. Notably, MPRO administration led to an increase in intestinal CD103⁺CD11b⁺ dendritic cells, promoting the induction of regulatory T cells and the robust suppression of inflammation in experimental disease settings. Our findings advocate the preference for bacterial consortia over single strains in the treatment of inflammatory disorders, carrying potential clinical relevance.

Lee C, et al. Immune Netw. 2023 Feb;23(1):e7. https://doi.org/10.4110/in.2023.23.e7

Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1− CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate–induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.