Human bodies host complex communities of microorganisms that adapt to different environments, from the gut to other body sites. This study leverages new chemical information from multi-omics datasets to understand how bacterial proteins change in response to two critical factors: oxygen and water availability. Chemical features of proteins were quantified by a computational approach that combines reference genomes with microbial abundances to assess community-level trends. We discovered that microbial proteins vary across different body sites, with the gut presenting unique characteristics. First, gut bacterial proteins have lower water content compared to bacteria in other body areas. This suggests that the intestinal environment drives specific evolutionary adaptations. Second, in patients with inflammatory conditions like COVID-19 and inflammatory bowel disease (IBD), gut bacterial proteins show distinctive chemical changes. Despite the oxidizing conditions associated with gut inflammation, bacterial proteins become more chemically reduced due to the shifting abundances of different types of bacteria. This unexpected result leads to the insight that some bacteria that typically thrive in oxygen-free environments (anaerobic bacteria such as Faecalibacterium) have more oxidized proteins than those in aerotolerant bacteria. This can help anaerobes survive and compete when the gut’s chemical conditions become more challenging during inflammation. By applying advanced computational techniques to a large collection of microbial community datasets, this research reveals that bacterial genomes actively evolve to survive in specific chemical conditions.