We found one example of an obesity-inducing strain in a human gut opportunistic species, Enterobacter cloacae, which is known to cause bacteremia when translocated into the bloodstream of immune-compromised individuals [42]. In a volunteer with 174.9 kg initial bodyweight, this species was found to comprise nearly 30 % of the total gut bacterial populations. After taking a dietary intervention aimed at modulating the gut microbiota, this species was almost non-detectable in the gut and the volunteer lost more than 50 kg of baseline bodyweight over 23 weeks, along with recovery of all parameters of metabolic syndrome. A strain named B29 was isolated from the volunteer’s baseline fecal sample and was confirmed to be a member of the overgrowing species of E. cloacae. When inoculated into the gut of germ-free C57/B6 mice fed on a high-fat diet, B29 induced fully developed obesity phenotypes, including inflammation, adiposity and insulin resistance. B29 colonization was also shown to be able to reduce the expression level of Fiaf in the ileum and promote the expression of Acc1 and Fas in the liver. B29-colonized mice fed on normal chow or germ-free control mice fed on a high-fat diet did not become obese. Only the combination of a high-fat diet and mono-association of B29 led to elevated endotoxin levels in the serum and systemic inflammation, and local inflammation in the liver and fat pads. This is the first reported example in which a single strain can induce fully developed obesity phenotypes in gnotobiotic mice. This strain was thus identified as an obesity-inducing “pathogen” by following the logic of Koch’s postulates.
