Gut microbiome in obesity and associated metabolic disorders in children and adolescents

Abstract

The paediatric obesity epidemic is one of the greatest health crises of our time. Despite concerted efforts, this unprecedented health issue remains unresolved. Most treatments for obesity have been relatively unsuccessful and there is an urgent need for alternative treatment paradigms. The gut microbiome is increasingly recognised to play an important role in the maintenance of health and prevention of diseases. The central hypothesis of this thesis is that gut dysbiosis is a risk factor for obesity, and modulation of the gut microbiome utilising faecal microbiome transfer (FMT) may be an effective treatment for adolescent obesity and metabolic diseases. This hypothesis was tested in 2 studies, the first indirectly by examining the associations between early life exposure to antibiotics and childhood obesity; and the second more directly by evaluating the effectiveness of FMT to reduce weight and improve metabolism among adolescents with obesity. The first was a large retrospective cross-sectional study evaluating the associations between antibiotics exposure in women during pregnancy and in their children early in life and childhood obesity. Whilst initial overall analyses demonstrated an association between greater antibiotics exposure and childhood obesity, further analyses on siblings and twins showed no such associations. Thus, while judicious use of antibiotics is important, exposure to antibiotics is unlikely to be a major risk factor for obesity. The second study was a randomised double-blind placebo-controlled trial (Gut Bugs Trial), which examined the effectiveness of FMT to treat obesity and improve metabolism among adolescents. FMT did not lead to weight loss, but led to sustained reduction in abdominal adiposity and changes in gut microbiome composition. Post-hoc analyses indicated that FMT was associated with a marked reduction in metabolic syndrome among participants with this undiagnosed condition at baseline. Overall, FMT without strict regulation of diet appears ineffective for weight loss, but may be effective to reduce abdominal adiposity, and may be a potential treatment for metabolic syndrome. Future larger trials are needed to confirm these results, and identify the bacteria and the metabolic pathways associated with improved health outcomes.