Beta-lactamases in anaerobic, intestinal bacteria: a narrative review

Anaerobic bacteria in the human intestinal microbiota play a pivotal role in antibiotic resistance, primarily through the production of β-lactamases. This narrative review explores the diversity of β-lactamases found in intestinal anaerobes, their functional characteristics, and clinical implications. Species of the genus Bacteroides are major producers, harboring enzymes from Ambler classes A (e.g. CepA, CfxA and CblA), B (e.g. CfiA and CcrA) and D (e.g. OXA-347), with activity ranging from cephalosporinases to carbapenemases and oxacillinases. Other gut members, including Clostridioides difficile , Fusobacterium nucleatum , and Acidaminococcus fermentans , also encode specific β-lactamases. These enzymes contribute to microbiota resilience following β-lactam exposure and can protect neighboring bacteria via extracellular degradation. This protective mechanism has inspired therapeutic applications, such as recombinant β-lactamases (ribaxamase, SYN-006) designed to preserve gut integrity during antibiotic therapy. Understanding these intrinsic resistance mechanisms is essential for optimizing antibiotic stewardship and mitigating the spread of resistance genes. • Intestinal anaerobes produce diverse β-lactamases from Ambler classes A, B, and D • Structure-based methods reveal novel β-lactamase genes with low sequence identity to known ARGs • β-lactamases protect the microbiota by degrading β-lactams residues • β-lactamase activity correlates with microbiota resilience after β-lactam exposure • Recombinant β-lactamases (e.g., ribaxamase) show promise in preventing β-lactam -induced dysbiosis