Biology subjects

Beliaeva, M. A.

Publications and source records attributed to Beliaeva, M. A..

2 recordsLinked to original sources

bioRxiv2026

Bacterial metabolism of synthetic steroids across ecosystems reveals diverse biotransformation products, reactions, and enzymes

Biotransformation of synthetic steroid drugs by gut and environmental bacteria affects their activity within the host, persistence, and environmental fate of these widely used pharmaceuticals. However, the spectrum of bacterial transformation of synthetic steroids, the enzymes involved, and the role of cooperative microbial metabolism in these processes remain poorly understood. We systematically mapped the biotransformation of 22 steroids, comprising 20 synthetic and 2 natural compounds and spanning clinically used estrogens, progestogens, corticosteroids, and prodrugs, across 12 bacterial species (8 intestinal and 4 environmental), yielding 264 steroid-bacteria combinations. We identified 97 unique biotransformation products and found that the tested bacteria catalyze diverse reactions including ester hydrolysis, oxidation-reduction chemistry, and steroid side-chain cleavage. Notably, the environmental bacterium Sphingobium herbicidovorans catalyzed desmolase-like steroid side-chain cleavage under aerobic conditions, a transformation previously reported solely for anaerobic bacteria. Combining sequence homology searches, a genetic gain-of-function screen, and expression proteomics we identified six steroid-transforming enzymes in S. herbicidovorans. We further demonstrate that distinct bacterial species cooperatively metabolize synthetic steroids through cross-feeding, enabling sequential activation and metabolism of corticosteroids across microbial communities. Together, our findings uncover previously unrecognized bacterial enzymes and community-level interactions involved in synthetic steroid metabolism. By directly linking steroid metabolites, enzymes, and microbial community interactions, this study provides molecular-level mechanistic insights into microbial steroid biotransformation. Such insights are essential for ultimately predicting metabolic interactions within and across microbial communities, as well as their interactions with the host and the environment.

microbiology↗

bioRxiv2026

Lithocholic acid modulates the growth of butyrate-producing bacteria and is decreased in the feces of stunted children

Bile acids modulate the intestinal microbiota and serve as key signaling molecules in host physiology. Bile acid dysregulation has been implicated in nutritional and inflammatory diseases; however, data on the pool of bile acids present in stunted children or children suffering of environmental enteric dysfunction (EED) is limited, particularly in the upper intestinal compartment where disease phenotypes are most relevant. In this study, we performed a targeted metabolomics approach on 75 bile acids and their derivatives, including gastric and duodenal aspirates and fecal samples from almost 1000 children from two Sub-Saharan cities. We found that levels of secondary bile acids, especially lithocholic acid, are significantly lower in the feces of stunted and EED children, while ursocholic acid and its derivatives are significantly higher. Levels of primary and sulfated bile acids are also increased in the feces of children with EED. Microbiota sequencing revealed that high lithocholic acid levels are positively associated with butyrate-producing bacteria, while negatively associated with oral taxa like Streptococcus and Veillonella. In vitro tests on a panel of reference strains showed that oral bacteria bioaccumulate and are inhibited by a variety of bile acids, while lithocholic and chenodeoxycholic acids modulate the growth of several butyrate-producing bacteria. This effect was even stronger with tauro- or glycol-conjugated bile acids. Exposing stool-derived in vitro communities from children in Afribiota to these bile acids confirmed their positive impact on butyrate producers and negative effect on overgrowing oral taxa. Our findings suggest that secondary bile acids, reduced in stunting and EED, modulate the growth of butyrate-producing bacteria while suppressing harmful oral taxa, highlighting their potential as tools to modulate microbiota composition.

microbiology↗