Gut Microbes最新文献

Colonization resistance is a fundamental host defense mechanism that relies on the synergistic interaction between the gut microbiota and the host immune system to prevent enteric pathogen colonization and infection. This review synthesizes current knowledge of the multifaceted mechanisms governing colonization resistance against intestinal pathogens. We examine how commensal microbes directly suppress pathogens through niche and nutrient competition, contact-dependent inhibition, and the production of antimicrobial compounds and metabolites. From the host perspective, we outline the essential roles of gut barriers, innate and adaptive immunity, and antimicrobial peptides in maintaining microbiota homeostasis while selectively restricting pathogen expansion. We also emphasize the role of IL-22 signaling and its regulation of epithelial glycosylation, which modulates nutrient availability and shapes microbial competitiveness. Finally, we discuss key challenges and future research directions in colonization resistance and related translational research, with the goal of informing novel strategies to prevent and treat intestinal infections and inflammatory diseases.

Aging is frequently accompanied by inflammaging-a chronic, low-grade inflammatory state that contributes to functional decline and disease risk. Disruption of the intestinal barrier is increasingly being recognized as a key driver of inflammaging; however, its relationship with the gut microbiota in older adults remains poorly understood. Here, we demonstrate a significant association of intestinal barrier dysfunction markers with systemic inflammatory markers using a cross-sectional study in this population. Notably, the genus Parabacteroides showed a strong negative association with barrier dysfunction. In vitro assays showed that three Parabacteroides lineages predominant in older adults, including P. merdae, enhanced the intestinal barrier integrity in a viability-dependent manner. Fecal sialic acid (Neu5Ac) levels were positively correlated with the abundance of Parabacteroides. Mediation analysis further indicated that Parabacteroides significantly mediated the association between fecal sialic acid and intestinal barrier markers. Culture experiments showed that both sialic acid and mucin, which is rich in terminal sialyl residues, promoted Parabacteroides growth. Transcriptomic analysis of P. merdae cultured with sialic acid revealed upregulation of genes for sialidases, transporters, and enzymes, consistent with sialic acid catabolism and transport, suggesting utilization of mucin-derived sialic acid. Together, these findings indicate that in older adults, Parabacteroides is linked to the intestinal barrier integrity and responds to mucin-associated sialic acid, supporting a model wherein host-derived glycans foster barrier-protective microbes to promote healthy aging. The study findings provide avenues for devising strategies for maintaining the intestinal barrier integrity and reducing age-related inflammation, which may ultimately contribute to the prevention of inflammaging.

Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation and occurs when T cells from the donor graft target recipient-derived antigen on host tissue. The involvement of the gastrointestinal (GI) tract drives morbidity and mortality-not coincidentally, the GI tract also harbors the most complex and abundant human microbial reservoir. In this review, we first revisit how the microbiota initiates, propagates, and protects against GvHD in the context of both innate and adaptive immunity. Historically, the impact of the microbiota on GvHD has been ascribed primarily to the activation of innate immunity, setting the stage for donor alloreactivity. Although established models of GvHD focus on donor-host genetic disparity as the principal driver of donor T-cell activation, commensal microbes in the GI tract, whose collective gene content exceeds that of the human genome by more than two orders of magnitude, constitutes an immense and poorly understood source of potential T-cell antigens. We next discuss the evolution of therapeutic approaches aimed at modifying the microbiota to improve GvHD outcomes, incorporating over 40 clinical studies spanning the last 40 years, from broad decontamination strategies to pre/probiotic approaches and targeted ecosystem replacement, including fecal microbiota transplantation.