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.
Highlights
Cachexia is a wasting syndrome characterized by adipose tissue and muscle atrophy [1,2,3]
To first investigate whether individuals suffering cancer-associated cachexia may benefit from consuming beneficial microbes, we tested the widely utilized ApcMIN mouse model predisposed to cancer cachexia [46]
By analyzing the gastrocnemius muscle of ApcMIN mice we found that feeding of L. reuteri in drinking water led to significantly (p < 0.05) larger gastrocnemius muscle masses [Figure 1A]
Summary
Cachexia is a wasting syndrome characterized by adipose tissue and muscle atrophy [1,2,3]. Cachexia has been associated with chronic inflammation, in particular involving neutrophils, such as in patients with COPD [4]. Mouse models, such as the ApcMin/+ [ApcMIN] mutant mouse of intestinal polyposis [6], have been utilized to study cancer-associated cachexia due to uncontrolled levels of Interleukin (IL)-6 and other host inflammatory responses [7,8,9,10]. In addition to numerous premalignant intestinal polyps and cachexia, ApcMIN mice display premature thymic involution [14] linked with their early demise at a very young age
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