Title: A Review of Segmented Filamentous Bacteria – Commensal Microbes with Potential Impact on Research Authors:

Segmented filamentous bacteria (SFB) are commensal bacteria first identified in the ileum of mice and rats. Morphologically similar bacteria have been reported in a broad range of host species, however all strains have been refractory to in vitro culture thus far. While SFB were once considered innocuous members of the intestinal microbiota of laboratory rodents, they have now been shown to impact the development of the immune system in rodents and, subsequently, the phenotype of models of both enteric and extraintestinal disease. Thus, SFB represent long-recognized commensal bacteria serving as an intercurrent variable in studies using rodent models of disease. Herein, we present the basic biology of SFB followed by a provocative discussion on the immunological and physiological effects of colonization with SFB, with particular attention to the impact on rodent models of disease. We also propose that SFB may represent the tip of the iceberg in our understanding of the influence of the microbiota on model phenotypes. As next-generation sequencing techniques are increasingly used to interrogate members of the microbiota refractory to culture, we are likely to identify other commensal microbes impacting the models we use. This review underscores the need to characterize such hostmicrobe interactions, as animal research represents a critical tool that is particularly vulnerable to scrutiny in an era of decreasing financial resources, and increasing accountability for the use of animal