Predatory bacteria as members of human microbiomes and their impact on gut diversity and homeostasis

Bdellovibrio and like organisms (BALOs) are obligate bacterial predators that shape microbial communities by promoting species diversity, yet they have long been considered irrelevant to the human gut due to their presumed obligate aerobic lifestyle. Here, we challenge this view through a combined meta-analytic, experimental, and conceptual investigation of BALOs in human microbiomes. Reanalyzing 168,000 consistently processed samples from the Human Microbiome Compendium spanning 482 studies, we detected BALOs in more than 80 studies and across multiple body sites worldwide, with a gut prevalence of 2.4%, a finding confirmed by reanalysis of the PRIME database for 16S rRNA microbiome data. Strikingly, BALO presence was consistently associated with higher microbial alpha-diversity across body sites and disease contexts. Biopsy-derived samples showed a substantially higher prevalence than fecal samples, suggesting a mucosa-proximal niche. Our laboratory experiments showed that multiple Bdellovibrio strains can delay the loss of microbial diversity in vitro and remain active under gut-relevant conditions, including 37C, pH 6.5, and in the presence of mucus. Genomic analyses further revealed terminal reductases, including nitrite reductases, in several BALO genomes, indicating the capacity for anaerobic or microaerobic respiration, consistent with persistence in mucosal microenvironments. Notably, the metabolic and ecological profiles of cultured BALOs closely match those of facultative anaerobes, which constitute their preferred prey and are central drivers of dysbiosis in inflammatory bowel disease, diabetes, colorectal cancer, and chronic kidney disease. Building on these findings, we propose a conceptual framework in which BALOs contribute to gut homeostasis by controlling the expansion of facultative anaerobes under inflammatory conditions, thereby facilitating the restoration of fermentative, butyrate-producing communities. Together, our results establish BALOs as consistent, functionally relevant members of the human microbiome and a promising natural candidate for therapeutic strategies targeting chronic gut disease.