Biology subjects

Jans, M.

Publications and source records attributed to Jans, M..

3 recordsLinked to original sources

bioRxiv2026

Indigenous Yanomami gut microbiota protects against diet-induced metabolic dysfunction

Industrialization profoundly alters the human gut microbiota, reducing microbial diversity and eliminating taxa prevalent in non-industrialized populations. These microbiota alterations accompanying industrialization might contribute to the increasing prevalence of obesity and other chronic inflammatory diseases, yet direct experimental evidence remains lacking. We compared the gut microbiota of Indigenous Brazilian Yanomami and urban Belgian donors and transplanted these into germ-free (GF) mice subjected to high-fat diet (HFD). The Yanomami microbiota exhibited greater richness and distinct composition enriched for VANISH (Volatile and/or Associated Negatively with Industrialized Societies of Humans) taxa. Transplantation of Yanomami microbiota significantly attenuated HFD-induced metabolic dysfunction, reducing weight gain, diabetes incidence, and promoting adipose and hepatic Th2 immunity. Yanomami-derived microbial communities displayed enhanced ecological stability and enrichment for short-chain fatty acid-associated taxa and metabolic functions post-HFD. Our findings demonstrate that the microbiota from low-urbanization populations confer protection against diet-induced metabolic disease, highlighting ecological resilience and specific microbial functions as potential targets for microbiota-inspired therapeutics.

microbiology↗

bioRxiv2023

Colibactin-induced genotoxicity and colorectal cancer exacerbation critically depends on adhesin-mediated epithelial binding

Various bacteria are suggested to contribute to colorectal cancer (CRC) development, including pks+ E. coli which produce the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells. It remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells and its DNA to cause harm. Using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC, we found that pks+ E. coli drives CRC exacerbation and tissue invasion in a colibactin-dependent manner. Using isogenic mutant strains, we further demonstrate that CRC exacerbation critically depends on expression of the E. coli type-1 pilus adhesin FimH and the F9-pilus adhesin FmlH. Blocking bacterial adhesion using a pharmacological FimH inhibitor attenuates colibactin-mediated genotoxicity and CRC exacerbation. Together, we show that the oncogenic potential of pks+ E. coli critically depends on bacterial adhesion to host epithelial cells and is critically mediated by specific bacterial adhesins. Adhesin-mediated epithelial binding subsequently allows production of the genotoxin colibactin in close proximity to host epithelial cells, which promotes DNA damage and drives CRC development. These findings present promising therapeutic avenues for the development of anti-adhesive therapies aiming at mitigating colibactin-induced DNA damage and inhibiting the initiation and progression of CRC, particularly in individuals at risk for developing CRC.

cancer biology↗

bioRxiv2023

Sterile triggers drive joint inflammation in TNF and IL-1beta dependent mouse arthritis models

Arthritis is the most common extra-intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed the gut-joint-axis. The clinical association between gut and joint inflammation is further supported by the success of common therapeutic strategies and microbiota dysbiosis in both conditions. Most data however support a correlative relationship between gut & joint inflammation, while causative evidence is lacking. Using two independent transgenic mouse arthritis models, either TNF or IL1{beta} dependent, we demonstrate that arthritis develops independently of the microbiota and intestinal inflammation, since both lines develop full-blown articular inflammation under germ-free conditions. In contrast, TNF-driven gut inflammation is fully rescued in germ-free conditions indicating that the microbiota is driving TNF-induced gut inflammation. Together, our study demonstrates that, although common inflammatory pathways may drive both gut and joint inflammation, the molecular triggers initiating such pathways are distinct in these tissues.

immunology↗