Moreover, the central role of sensing of LPS (66), elevated in serum as a consequence of microbiota dysbiosis and loss of gut barrier integrity in each of infection and obesity, conditions associated with chronic inflammation and ageing per se, underlines the key contributions of the TLR4/MyD88 signalling cassette and the gut-osteoimmunology axis in the (dys)regulation of health and well-being over the life-course (11–14, 17–19, 25, 69–71). This evidence concerns the gene TLR4 and obesity due to melanocortin 4 receptor deficiency.