Biology subjects

Schroeder, B. O.

Publications and source records attributed to Schroeder, B. O..

4 recordsLinked to original sources

bioRxiv2024

Antibiotics damage the colonic mucus barrier in a microbiota-independent manner

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not properly separate the host intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics might affect the integrity of the mucus barrier. By systematically determining the effects of different antibiotics on mucus layer penetrability we found that oral antibiotic treatment led to breakdown of the mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning and ex vivo mucus secretion measurements, we determined that antibiotic treatment induces ER stress in the colonic tissue which inhibits colonic mucus secretion in a microbiota-independent manner. This mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to development of intestinal inflammation by impeding mucus production.

immunology↗

bioRxiv2024

A history of repeated antibiotic usage leads to microbiota-dependent mucus defects

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and lastingly changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply-phenotyped Estonian Microbiome Cohort (EstMB) we here utilised human-to-mouse faecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex-vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilising bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterised by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our findings suggest that long-term antibiotic use in humans results in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

microbiology↗

bioRxiv2023

The gut commensal Blautia maintains colonic mucus function under low fiber consumption through short-chain fatty acid-mediated activation of Ffar2

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, our proof-of-concept study demonstrates that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

microbiology↗

bioRxiv2023

A multi-strategy antimicrobial discovery approach reveals new ways to combat Chlamydia

While the excessive use of broad-spectrum antibiotics is a major driver of the global antibiotic resistance crisis, more selective therapies remain unavailable for the majority of bacterial pathogens. This includes Chlamydia spp., which cause millions of urogenital, ocular, and respiratory infections each year. We here report major conceptual additions to the available toolkit for antichlamydial discovery, including both experimental and computational approaches. Moreover, we report the to date most comprehensive search of the chemical space for novel antichlamydial activities, which identified over sixty compounds that are chemically diverse, structurally different from known antibiotics, non-toxic to human cells, and highly potent in blocking Chlamydia growth. While some compounds caused a reversible block in Chlamydia development, others could eradicate both established and persistent infections in a bactericidal manner. The most potent antichlamydials displayed compelling selectivity, some also synergies with clinically used antibiotics, as well as interactions profiles enabling predictions of molecular modes of action. Moreover, one compound displayed reduced antichlamydial efficacy in autophagy-deficient cells, suggesting a host- targeted activity. Altogether, we suggest that these novel antichlamydials could serve as tools for advancing our understanding of Chlamydia biology and as chemical starting points for developing more sustainable therapeutics for one of the most successful groups of intracellular pathogens.

microbiology↗