Theriault, B. | bioRxiv Science

bioRxiv2025

Non-invasive approach for endoluminal biopsy coupled with single-cell proteomics allows for immune characterization of intracranial aneurysms

The immune regulatory mechanisms driving the stability, growth, and rupture of intracranial aneurysms (IAs) remain incompletely understood. In this study, we employ endoluminal biopsy with single-cell proteomics to comprehensively profile the immune landscape of IAs across their pathologic states. Our findings reveal distinct immune signatures associated with aneurysm states. Stable, i.e. non-growing unruptured, IAs exhibit a balanced immune cell composition. Ruptured IAs are marked by significant neutrophil predominance. Notably, we highlight key immune markers in aneurysm instability, offering new insights into immune drivers of aneurysm progression. These findings provide a foundation for immune-targeted, non-invasive therapeutic strategies aimed at targeting IAs and preventing rupture.

physiology↗

bioRxiv2023

Microbiota-dependent early life programming of gastrointestinal motility

Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.

physiology↗

bioRxiv2023

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) arise from a convergence of underlying genetic susceptibility, environmental factors, and shifts in gut microbiota function and membership. Although the latter may trigger and contribute to IBD, there is little consensus on a specific causative pathogen. In this study, we demonstrate that commensal Bacteroides fragilis strains from ulcerative colitis (UC) patients before and during the development of ileal pouchitis engraft and promote colitis in specific pathogen free (SPF) IL-10 deficient (IL-10-/-) mice, but not in wild type SPF mice or when mono-associated in germ free mice. The colitis in IL-10-/- mice was also associated with significant alterations in commensal microbiota potentially important for maintaining intestinal and immune homeostasis. UC pouchitis B. fragilis also engrafts in DSS-induced colitis in WT SPF mice, indicating a fitness advantage under conditions of mucosal inflammation over other commensals in the gut microbiota. These findings show that gut inflammation promotes the expansion and fitness of UC-derived Bacteroides species that is associated with changes in the SPF gut microbiota and may be promote colitis in genetically susceptible hosts. ImportanceThis study supports the notion that human inflammatory bowel diseases arise from the emergence of indigenous pathobionts in genetically-prone subjects. Colitis-promoting pathobionts are well-suited to establish themselves in the host inflammatory environment and outcompete endogenous microbiota. Once engrafted, the pathobiont can further aggravate inflammation in a genetically-susceptible host. Such complex interplay among several factors creates a vicious pro-inflammatory cycle and promotes disease development. These findings are consistent with our previous clinical observation that B. fragilis, an otherwise low-abundance commensal species, expands prior to the development of UC pouchitis. We believe these findings are relevant to the pathogenesis of UC pouchitis and possibly human inflammatory bowel diseases in general, underscoring the role of commensal to pathobiont transitions, rather than classical pathogens, in promoting and exacerbating the onset of human IBD.

microbiology↗