Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont

Abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.

Keywords: Streptococcus agalactiae; gut microbiome; human microbiome; microbial ecology; pathogenesis.

Fig 1

Known body sites of GBS disease and asymptomatic carriage. Summary of the known body sites where (A) GBS causes invasive disease (3–11) and (B) the known body sites where GBS is an asymptomatic colonizer (12–16). Although GBS has not been cultured from the esophagus, stomach, and small intestine, Streptococci are abundant in these niches, as determined by 16S rRNA marker gene analysis (17, 18). Given that (i) GBS has been cultured from the mouth and more distal parts of the GI tract, (ii) GBS has the physiological capabilities to thrive in the environmental conditions in these niches, and (iii) adherence factors capable of interacting with host macromolecules found in these niches, we hypothesize that GBS also resides in these locations. Created with BioRender.com under agreement #RS26EQHEOE.

Fig 2

Prospects for therapeutics enabled by a better understanding of GI colonization. Summary of potential GBS-microbiome and GBS-host interactions that could be targeted with a better understanding of GBS in the GI tract. Created with BioRender.com under agreement #IEN263N1AK5.