Schattenberg, J. M. | bioRxiv Science

bioRxiv2025

Joint bacterial traces in the gut and oral cavity of Colitis patients provide evidence for saliva as rich microbial biomarker source

The human microbiome, distributed across various anatomical sites, holds promise for identifying diagnostic biomarkers and therapeutic targets in disease. In inflammatory bowel disease (IBD), including ulcerative colitis (UC), interactions between the gut and oral microbiomes are crucial for understanding disease mechanisms and guiding interventions. The IMAGINE study sequenced 1,931 specimens from saliva, plaque, stool, and other sources in patients and healthy controls. Here, we assess whether the oral (saliva/plaque) or gut microbiota provides greater diagnostic potential in IBD and examine shared dysregulation across sample types. Among 177 oral samples (102 healthy, 75 IBD) and 92 stool samples (57 healthy, 35 IBD), we identified 240 distinct strains in plaque, 229 in saliva, and 231 in stool, with 46 strains present in all three. Saliva showed a significantly higher average effect size (0.2) than stool (0.04) and plaque (0.06). Notably, Actinomyces sp., Bifidobacterium dentium, and Veillonella parvula exhibited increased effect sizes, suggesting their potential as diagnostic markers or therapeutic targets. These findings indicate that microbiome profiling in IBD may improve diagnostics and treatment strategies.

microbiology↗

bioRxiv2020

Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic lipid metabolism. We show that MSR1 induces a pro-inflammatory response via the JNK signaling pathway upon triggering by saturated fatty acids. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNFa. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and ex vivo human liver slices resulted in the prevention of foamy macrophage formation and liver inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate transaminase levels in a cohort of over 400,000 patients. Taken together, our data suggest a critical role for MSR1 in lipid homeostasis and a potential therapeutic target for the treatment of NAFLD. One Sentence SummaryThe immunometabolic role of MSR1 in human NAFLD.

immunology↗