Housing temperature plays a critical role in determining gut microbiome composition in research mice: Implications for experimental reproducibility

Preclinical mouse models are widely used for studying mechanisms of disease and responses to thera-peutics, however there is concern about the lack of experimental reproducibility and failure to predict translational success. The gut microbiome has emerged as a regulator of metabolism and immunological processes in health and disease. The gut microbiome of mice differs by supplier and this affects exper-imental outcomes. We have previously reported that the mandated, mildly cool housing temperature for research mice (22 & DEG;-26 & DEG;C) induces chronic adrenergic stress which suppresses anti-tumor immunity and promotes tumor growth compared to thermoneutral housing (30 & DEG;C). Therefore, we wondered how housing temperature affects the microbiome. Here, we demonstrate that the gut microbiome of BALB/c mice is easily modulated by a few degrees difference in temperature. Our results reveal significant dif-ferences between the gut microbiome of mice housed at 22 & DEG;-23 & DEG;C vs. 30 & DEG;C. Although the genera vary, we consistently observed an enrichment of members of the family Lachnospiraceae when mice are housed at 22 & DEG;-23 & DEG;C. These findings demonstrate that adrenergic stress and need for increased energy harvest to support thermogenesis, in addition to other factors such as diet, modulates the gut micro -biome and this could be one mechanism by which housing temperature affects experimental outcomes. Additionally, tumor growth in mice housed at 30 & DEG;C also increases the proportion of Lachnospiraceae. The idea that stress can alter the gut microbiome and cause differences in experimental outcomes is applicable to mouse studies in general and is a variable that has significant potential to affect experi-mental reproducibility.& COPY; 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).