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Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inter- and intra-species diversity in pathways that likely influence an isolate's ability to impact host health. These differences are likely to impact colonization resistance through lantibiotic expression or intestinal acidification, influence host mucosal immune cells and enterocytes via butyrate production, or contribute to synergism within a consortium by heterogenous polysaccharide metabolism. Identification of these specific functions could facilitate development of probiotic bacterial consortia that drive and/or restore in vivo microbiome functions., Competing Interests: Declaration of Interests E.G.P. has received speaker honoraria from Bristol-Myer Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis, and Ferring Pharmaceuticals; is an inventor on patent application no. WPO2015179437A1, entitled “Methods and compositions for reducing Clostridium difficile infection” and no. WPO2017091753A1, entitled “Methods and compositions for reducing vancomycin-resistant Enterococci infection or colonization”; and holds patents that receive royalties from Seres Therapeutics. The remaining authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)