Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5

Abstract

Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual’s risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.

Integrating nutrition and immunology: A new frontier

“…A key point is that in vertebrates this nutritional benefit is an emergent property of the activity of the total microbiota, rather than a benefit derived from one or two primary symbionts. Furthermore, the vertebrate gut microbiota are involved in many other aspects of host health and development (Bäckhed et al, 2005;Kau et al, 2011;Shin et al, 2011;Turnbaugh et al, 2008;Vijay-Kumar et al, 2010). Analyses of commensal host-microbial relationships in the intestine of mammalian models have identified microbial roles in the regulation of genes in many host systems, including development, differentiation, immunity and metabolism (Backhed et al, 2004;Hooper et al, 2001).…”

“…The increased incidence of modern lifestyle diseases such as allergies, diabetes, inflammatory bowel diseases and obesity to epidemic levels strongly links changes in nutrition, gut microbiota and immune function. (Backhed et al, 2004;Ley et al, 2006;Noverr and Huffnagle, 2004;Vijay-Kumar et al, 2010;Wen et al, 2008).…”

Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome

“…An increasing number of human studies have supported a link between certain gut microbiota signatures and obesity-related disorders [62][63][64]. However, it is still not fully understood how microbiota interact with the human body, and, consequently, how they affect metabolic homeostasis.…”

Les Japonais et nous

“…La flore intestinale des coprolithes ou des sujets momifiés pourrait nous éclairer. Outre l'intérêt croissant des variations de flores intestinales selon l'alimentation, en particulier dans les études sur l'obésité [6], et l'exemplarité de l'alimentation nippone qui n'est sans doute pas pour rien dans la longévité des Japonais, ce travail laisse entrevoir l'incroyable réseau que les êtres vivants sont capables de tisser entre eux à travers le temps et l'espace. ‡ The Japanese and us 2 Ce n'est que vers l'époque de la restauration de Meiji, à la fin du XIX e siècle, que la consommation de viande fut permise, voire encouragée.…”