A new study shows that protein sequences associated with microbial communities in the human gut have uniquely low stoichiometric water content and undergo counterintuitive chemical shifts toward chemically reduced states during inflammation, offering fresh insights into microbe–host interactions.
Microbial communities inhabit distinct chemical environments throughout the human body, from oxygen-rich skin to the water-absorbing gut.
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In a paper published this week in Biomedical Informatics, Jeffrey M. Dick of Central South University in China reports a novel “geochemical biology” approach that quantifies stoichiometric water (nH2O) and oxygen (nO2) content of proteins based on their elemental composition, revealing how these chemical features vary among microbial communities across body sites and in inflammatory diseases such as COVID-19 and inflammatory bowel disease (IBD).
“This is the first study to translate protein sequences from genomes of human-associated microbes into multiple chemical coordinates reflecting environmental pressures,” says Dr. Dick. “We find that gut bacterial proteins are intrinsically lower in stoichiometric water content, suggesting evolutionary tuning to the intestine’s water-absorbing environment.”
Human microbiomes
Using 16S rRNA gene surveys combined with reference proteomes, the study generated community reference proteomes for nasal, oral, skin, and gut microbiomes. The chemical metrics were validated against shotgun metagenomes and metaproteomes from independent datasets.
Key findings include:
- Distinct gut signature: Gut bacterial proteins exhibit lower nH2O than those from skin or oral sites, reflecting possible shaping by the intestine’s water-absorbing function.
- Inflammation-driven reduction: Contrary to expectations, proteins in gut microbiomes from COVID-19 and IBD patients are more chemically reduced (lower nO2) compared to healthy controls, driven by shifts in bacterial abundances.
- Role of anaerobes: Although obligate anaerobes like Faecalibacterium decline during inflammation, their more oxidized proteomes mean that their loss contributes to community-wide chemical reduction.
“These surprising results highlight that microbial community chemistry is shaped not only by environments but also by competitive dynamics among bacteria,” explains Dr. Dick. “Anaerobes face challenges under oxidative conditions associated with inflammation, while aerotolerant species expand to fill the gap. However, common gut anaerobes actually have relatively oxidized proteomes, so their depletion drives overall reduction at the community level.”
Body sites
The study leverages the chem16S R package and analyzes over 40 datasets spanning multiple body sites and inflammatory conditions, providing a computational framework for future investigations into host-microbe chemical interactions.
By linking protein chemistry to microbial ecology, this work offers a new perspective on dysbiosis and disease. “Tracking water and oxygen stoichiometry in microbial proteins could become a tool for monitoring how microbial communities respond to changing physiological conditions,” suggests Dr. Dick.
The author acknowledges limitations, including reliance on reference genomes and the predominant use of fecal samples, which cannot capture the spatial complexity of the gut’s oxygen and water gradients. The study proposes direct elemental analyses of microbial proteins and spatially resolved sampling along the gut as important future directions.
Fine-tuning protein sequences
This research bridges multiple scientific domains, combining techniques from microbiology and genomics with chemical data analysis to reveal how microorganisms fine-tune their protein sequences for survival in specific host environments. The findings suggest that chemical variables like oxygen levels and water availability are active drivers of microbial evolution, not merely passive background factors.
This paper was published in Biomedical Informatics (ISSN: 3005-3854), an online multidisciplinary open access journal led by Editor-in-Chief, Prof. Wing Kin Sung from Chinese University of Hong Kong.
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