Infection trains the host for microbiota-enhanced resistance to pathogens.

The microbiota shields the host against infections in a process known as colonization resistance. How infections themselves shape this fundamental process remains largely unknown. Here, we show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid taurine. Notably, supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. As such, pharmaceutical sequestration of sulfide perturbs the microbiota's composition and promotes pathogen invasion. Together, this work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train the microbiota, promoting its resistance to subsequent infection.

Microbiota configuration determines nutritional immune optimization.

Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes the expansion of commensal Bifidobacteria within the large intestine, which produce the short-chain fatty acid acetate. Acetate conditioning of the myeloid compartment during DR enhances the capacity of these cells to kill pathogens. Enhanced host protection during DR is compromised when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function play an important role in determining immune responsiveness to this dietary intervention. Altogether, our study supports the idea that DR induces both memory T cells and the gut microbiota to produce distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings suggest that nutritional cues can promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.

Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.

Background: Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. Objectives: 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models. Design: 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study. Results: We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. Conclusion: We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

MAIT cells are imprinted by the microbiota in early life and promote tissue repair.

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

Genotypic characterization of Porphyromonas gingivalis isolated from subgingival plaque and blood sample in positive bacteremia subjects with periodontitis.

AIM: The objective of this study was to investigate clonal relationship among Porphyromonas gingivalis isolated from subgingival plaque and blood samples in positive transient bacteremia subjects with periodontitis. MATERIAL AND METHODS: Unrelated patients with general chronic periodontitis or general aggressive periodontitis requiring scaling and root planing (SRP) were included in the study. Genotyping of each isolate was performed using pulsed field gel electrophoresis technique. Genetic relatedness of strains isolated within an individual or between different patients was determined by dendogram analysis. RESULTS: Following SRP, from 16 patients, seven patients showed positive P. gingivalis bacteremia and nine were negative. Thirty-two strains were isolated from subgingival plaque and blood samples before and during induced transient bacteremia. The majority of the patients harboured one clonal type. Two patients showed different clones in plaque and blood samples suggesting that more than one clone can be found in subgingival plaque. P. gingivalis isolates from periodontitis patients after transient bacteremia following SRP, revealed a high heterogeneity among isolates. CONCLUSION: In 6/16 subjects the same P. gingivalis isolate was found in the blood and in oral cavity. P. gingivalis heterogeneity suggests no association of a unique clonal type with transient bacteremia.