Fermentable Carbohydrates, Gut Microbiota and Health: an epidemiological approach – FeCaMic

Over the past decade, the microbiota has received an exponentially growing attention from the scientific community and the public as its role in human physiology was gradually being uncovered. In particular, gut microbial signatures were observed in various disease states, including obesity, diabetes, gastrointestinal disorders, colorectal cancer or neurodegenerative diseases, suggesting unbalanced host-gut microbiota interactions. Although the gut microbiota is considered as key for human health, the mechanisms involved and the definition of what constitutes a healthy gut microbiota remain important challenges to tackle. The gut microbiota feed on the fermentation of compounds brought by the human diet that are not or poorly absorbed in the small intestine and that end up more or less intact in the colon. Many such compounds belong to the family of carbohydrates and can be categorized as fibres (e.g., non-starch polysaccharides, resistant oligosaccharides, resistant starch) or FODMAPs (Fermentable Oligosaccharides (FOS and GOS), Disaccharides (lactose), Monosaccharides (fructose) and Polyols (ex. sorbitol, xylitol)). Fermentable carbohydrates therefore encompass a vast diversity of compounds (e.g., type and number of units, type of linkage, length) differing in their biological, physical and chemical properties as well as their physiological effects but also their interaction with the gut bacteria (e.g., selection of specialized bacterial species). These compounds are provided by various sources, each supplying a specific mix of fermentable carbohydrates: they can be naturally supplied by cereal products, fruit, vegetables, legumes, nuts or dairy products (lactose), but can also come from industrially processed foods where isolated fermentable carbohydrates (extracted from foods or synthesized) can be added to foods (as ingredients or additives) for technological purposes and/or to increase the fibre content. Different types of fermentable carbohydrates are likely to have differential effects on the gut microbiota and health outcomes. Indeed, while dietary fibres are generally associated to better health outcomes (e.g., obesity, colorectal cancer), FODMAPs have been studied almost exclusively in the context of irritable bowel syndrome where they were defined based on adverse gastrointestinal effects. Besides, the gut microbiota profile is likely to influence how fermentable carbohydrates will be associated with health outcomes. So far, no large-scale study has considered the whole range of fermentable carbohydrates and how they are combined in “real” individual diets in relation to gut microbiota and health outcomes, including i) whether fermentable carbohydrates come from whole foods or are provided as ingredients/additives in industrially-processed foods, ii) whether different profiles of fermentable carbohydrate intakes associates with different profiles of gut microbiota and health outcomes, iii) whether gut microbiota profiles mediate or modulate the association between fermentable carbohydrates and health. Hence, using the NutriNet-Santé cohort (N=170,000), the FeCaMic project will: 1) provide an in-depth characterisation of the profiles of intakes of fermentable carbohydrates, considering their various types and sources, and including those added as additives or ingredients, or consumed as dietary supplements; 2) investigate the associations between the detailed profiles of fermentable carbohydrate intakes and gut microbiota profiles in a large population-based sample (N=6,000 with stool samples collected and gut microbiota profiles sequenced), also taking into account the overall diet and other individual characteristics; 3) explore the mediation and modulation by the gut microbiota of the associations between the profiles of intakes of fermentable carbohydrates and two health outcomes relevant to both fermentable carbohydrates and the gut microbiota: weight status and gastrointestinal disorders.