Biology subjects

Mahmood, S. D.

Publications and source records attributed to Mahmood, S. D..

3 recordsLinked to original sources

bioRxiv2026

Oral Gut Microbial Axis in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

The oral cavity is increasingly recognized as a reservoir of microbes that can translocate to and influence the gut microbiome. This oral-gut microbial axis may contribute to the pathogenesis of chronic gastrointestinal and hepatobiliary disorders, including inflammatory bowel disease (IBD) and its comorbidity, primary sclerosing cholangitis (PSC). To investigate the oral-gut microbial axis in IBD and PSC, we enrolled 191 participants spanning Crohns disease (CD), ulcerative colitis (UC), CD with PSC (CD-PSC), UC with PSC (UC-PSC), and healthy controls. We generated and analyzed the whole-metagenome shotgun sequencing data from saliva, tongue swabs, and fecal samples. Across oral and gut niches, we identified multiple microbial species differentially enriched in participants with UC compared with healthy controls, including Fusobacterium nucleatum and Gemella sanguinis in saliva, Catonella massiliensis and Tannerella serpentiformis on the tongue, and G. sanguinis and Sellimonas intestinalis in feces. Paired oral-gut analyses revealed 15 potential oral-origin species enriched in fecal samples; notably, G. sanguinis and Veillonella rogosae were consistently enriched in participants with UC. These findings were further supported by an external validation dataset comprising 1,716 gut metagenomes from five independent IBD cohorts, highlighting the reproducibility of oral microbial signatures. In exploratory analyses, smoking history was associated with shifts in the oral microbiome toward a UC-like state in healthy controls, suggesting a possible environmental modifier of the oral-gut microbial axis. Collectively, our study identifies distinct oral microbial signatures and their potential translocation to the gut in IBD and PSC, underscoring the role of the oral- gut microbial axis in disease progression.

microbiology↗

bioRxiv2025

A glycan atlas of the mammalian intestine through ontogeny and inflammation

The muco-epithelial interface in the mammalian gut is composed of a mucus and epithelial lining fundamental to barrier function, microbe-host interactions, and intestinal homeostasis. This barrier is heavily glycosylated by O-linked sugars covalently linked to mucin glycoproteins, and N-linked sugars that coat epithelial surface proteins. Gut O- and N-glycans are thought to play central roles in barrier function, host defense, nutrition and attachment for commensals and pathogens, immunoregulation and cell-cell interactions. However, the precise nature of the glycans and how glycan composition changes through development, as a function of diet, and during inflammation, remains incompletely understood. Here, we apply O- and N-glycomic platforms to profile glycans on mucus and intestinal epithelium. By mapping individual glycan species spatially and temporally we identify 57 O- and 18 N-glycans in the mouse intestine, and observe that fucosylation and sialylation varies according to intestinal region and developmental stage. We identify a subset of glycans regulated by the gut microbiome, and observe a constriction of the glycan repertoire during inflammation in both mice and humans. Together, these results provide an atlas of individual intestinal glycans and their dynamic range through ontogeny and inflammation, and represent a significant resource for our understanding of the role of intestinal glycans in health and disease and glycan-focused therapies for intestinal inflammation and shaping the gut microbiome. Highlights- Individual glycans vary across gut region and developmental stage - Terminal fucose and sialic acid residues vary across space and time - The microbiome influences gut glycan composition early in life - Gut inflammation in mice and humans converge on a restricted glycan repertoire eTOC blurbMicrobes colonizing the mammalian intestines encounter mucus and an epithelial layer highly decorated by glycans. Siegel et al. use glycomics to map these sugars in high resolution across gut region, microbial colonization, development and inflammation in both humans and mice.

microbiology↗

bioRxiv2024

Cultured Bacteria Isolated from Primary Sclerosing Cholangitis Patient Bile Induce Inflammation and Cell Death

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and progressive fibrosis of the biliary tree. The pathogenesis of PSC remains poorly understood, and there are no effective therapeutic options. Previous studies have observed associations between changes in the colonic and biliary microbiome and PSC. We aimed to determine whether bacterial isolates cultured from PSC patient bile induced disease-associated phenotypes in cells. MethodsBile was collected from PSC patients (n=10) by endoscopic retrograde cholangiography and from non-PSC controls (n=3) undergoing cholecystectomies. Biliary bacteria were cultured anaerobically, and 50 colonies per sample were identified by 16S rRNA sequencing. The effects of supernatants from seven PSC-associated bacterial strains on cellular phenotypes were characterized using human colonic (Caco-2), hepatic (HepG2), and biliary (EGI-1) cells. ResultsNo bacteria were isolated from non-PSC controls, while bacteria were cultured from most PSC patients. The PSC bile microbiomes exhibited reduced diversity compared to the gut or oral cavity, with one or two bacterial strains predominating. Overall, PSC-associated bacteria produced factors that were cytotoxic to hepatic and biliary cells. Enterococcus faecalis, and to a lesser extent Veillonella parvula, induced epithelial permeability, while Escherichia coli, Fusobacterium necrophorum, and Klebsiella pneumoniae induced inflammatory cytokines in biliary cells. ConclusionsOur data suggest that bacteria cultured from PSC bile induce cellular changes that may contribute to PSC disease pathogenesis. Enterococcus may promote intestinal permeability, facilitating bacterial migration to the biliary tree. Once there, Escherichia, Fusobacterium and Klebsiella, may cause inflammation and damage in biliary and liver cells.

microbiology↗