Protective effects of Mycobacterium vaccae ATCC 15483 against "Western"-style diet-induced weight gain and visceral adiposity in adolescent male mice

Luke W Desmond; Lamya'a M Dawud; Lyanna R Kessler; Tyler Akonom; Elizabeth A H Hunter; Evan M Holbrook; Nathan D Andersen; John D Sterrett; Dennis A Boateng; Barbara J Stuart; Lucas Guerrero; Matthew J Gebert; Pei-San Tsai; Dominik Langgartner; Stefan O Reber; Matthew G Frank; Christopher A Lowry

doi:10.1016/j.bbi.2024.12.029

Protective effects of Mycobacterium vaccae ATCC 15483 against "Western"-style diet-induced weight gain and visceral adiposity in adolescent male mice

Brain Behav Immun. 2024 Dec 19:S0889-1591(24)00758-X. doi: 10.1016/j.bbi.2024.12.029. Online ahead of print.

Authors

Luke W Desmond¹, Lamya'a M Dawud², Lyanna R Kessler³, Tyler Akonom⁴, Elizabeth A H Hunter⁵, Evan M Holbrook⁶, Nathan D Andersen⁷, John D Sterrett⁸, Dennis A Boateng⁹, Barbara J Stuart¹⁰, Lucas Guerrero¹¹, Matthew J Gebert¹², Pei-San Tsai¹³, Dominik Langgartner¹⁴, Stefan O Reber¹⁵, Matthew G Frank¹⁶, Christopher A Lowry¹⁷

Affiliations

¹ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: luke.desmond@colorado.edu.
² Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: lamyaa.dawud@colorado.edu.
³ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: lyanna.kessler@colorado.edu.
⁴ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: tyler.akonom@colorado.edu.
⁵ Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: elizabeth.hunterjr@colorado.edu.
⁶ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: evan.holbrook@colorado.edu.
⁷ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: nathan.d.anderson@colorado.edu.
⁸ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: john.sterrett@colorado.edu.
⁹ Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: dennis.boateng@colorado.edu.
¹⁰ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: barbara.stuart@colorado.edu.
¹¹ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: lucas.guerrero@colostate.edu.
¹² Department of Ecology and Evolutionary Biology, Cooperative Institute for Research in Environmental Sciences (CIRES), University of Colorado Boulder, Boulder, CO 80309, USA; Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: matthew.gebert@colorado.edu.
¹³ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: pei-san.tsai@colorado.edu.
¹⁴ Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, Ulm, Germany. Electronic address: dominik.langgartner@uni-ulm.de.
¹⁵ Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, Ulm, Germany. Electronic address: stefan.reber@uni-ulm.de.
¹⁶ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: matt.frank@colorado.edu.
¹⁷ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: christopher.lowry@colorado.edu.

PMID: 39709061
DOI: 10.1016/j.bbi.2024.12.029

Abstract

The prevalence of noncommunicable inflammatory disease is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapeutic strategies are needed to effectively deal with this issue. One promising approach is leveraging microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory, immunoregulatory, and stress-resilience properties. This study aimed to assess whether weekly subcutaneous administrations of a whole-cell, heat-killed preparation of M. vaccae ATCC 15483 (eleven injections initiated one week before the onset of the diet intervention), relative to vehicle injections, in adolescent male C57BL/6N mice can mitigate inflammation associated with Western-style diet-induced obesity, which is considered a risk factor for a number of metabolic and inflammatory diseases. Our results show that treatment with M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations. The Western-style diet, relative to a control diet condition, decreased alpha diversity and altered the community composition of the gut microbiome, increasing the Bacillota to Bacteroidota ratio (formerly referred to as the Firmicutes to Bacteroidetes ratio). Despite the finding that M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations, it had no effect on the diversity or community composition of the gut microbiome, suggesting that it acts downstream of the gut microbiome to alter immunometabolic signaling. M. vaccae ATCC 15483 reduced baseline levels of biomarkers of hippocampal neuroinflammation and microglial priming, such as Nfkbia and Nlrp3, and notably decreased anxiety-like defensive behavioral responses. The current findings provide compelling evidence supporting the potential for M. vaccae ATCC 15483 as a promising intervention for prevention or treatment of adverse immunometabolic outcomes linked to the consumption of a Western-style diet and the associated dysbiosis of the gut microbiome.

Keywords: Anxiety; Firmicutes:Bacteroidetes ratio; Hygiene hypothesis; Neuroinflammation; Obesity; “Old Friends” hypothesis.