title: Beneficial bacteria inhibit cachexia.
abstract: Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Varian
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Sravya
authors.initials: S
authors.lastname: Gourishetti
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.|Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lakritz
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Levkovich
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Kwok
authors.affiliation: Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Teliousis
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Yassin M
authors.initials: YM
authors.lastname: Ibrahim
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Sheyla
authors.initials: S
authors.lastname: Mirabal
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Erdman
mesh_terms: D000818:Animals; D002100:Cachexia / Q000382:microbiology / Q000517:prevention & control*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D052200:Limosilactobacillus reuteri / Q000502:physiology*; D008136:Longevity; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000494:pharmacology*; D055948:Sarcopenia / Q000382:microbiology / Q000517:prevention & control*; D013950:Thymus Gland / Q000166:cytology / Q000382:microbiology
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein
keywords: cachexia; inflammation; microbe; probiotic; sarcopenia