Weight loss diets have been tested for decades aiming at finding effective treatments to combat the continuing rise in obesity prevalence. However, studies consistently show that there is large variation in weight loss success among participants following such interventions. Several individual characteristics such as host genes and gut microbiota may help increase our understanding of why
some subjects respond to a given weight loss diet and others do not. A compositional pattern of the microbiota, enterotypes, has during the last decade been associated with both dietary intake and metabolic health. Recently, enterotypes were also linked to weight loss success, as individuals with the Prevotella enterotype was shown to lose weight on a New Nordic diet, rich in fiber, while the group with a Bacteroides enterotype remained weight stable on the same diet.
Accordingly, the overall objective of this PhD thesis was to explore the potential of microbial enterotypes as biomarkers to individualize dietary treatment in obesity. More specifically, two independent studies examine whether enterotypes can predict weight loss among overweight individuals following consumption of high fiber diets compared to a control diet. The three objectives
and consequent papers are described below:
1. To review the existing literature on enterotype stratification in dietary and medical interventions
2. To investigate weight loss success between enterotypes following whole grain consumption, and to explore if starch digestion in the upper gastrointestinal tract influences these potential enterotype-weight loss associations
3. To examine weight loss success between enterotypes following whole grain fiber (arabinoxylanoligosaccharide) consumption and correlate relevant bacterial species with host metabolism

In Paper 1, we concluded that high-fiber diets seems to promote weight loss among Prevotella enterotype subjects, but not among Bacteroides enterotype subjects. In contrast, increasing bifidobacteria abundance in the gut for the Bacteroides enterotype appears to improve metabolic parameters, suggesting that this approach should be tested as an alternative weight loss strategy.

In Paper 2, we found that overweight adults with high Prevotella abundances lost more weight than individuals with low abundances of Prevotella, when consuming whole grains ad libitum. Moreover, the digestive capacity for starch degradation (amylase gene, AMY1) was found to mediate the weight loss predictability of Prevotella, as it was only among the participants with a low AMY1 copy number that Prevotella was linked to weight loss, and thus, not among the participants with a high AMY1 copy number.

In Paper 3, a Bacteroides species was found to be a better predictor of body weight regulation than the proxy of enterotypes, Prevotella-to-Bacteroides ratio, following consumption of whole grain fibers (arabinoxylan-oligosaccharides). Also, this data revealed a potentially new subtype of the Bacteroides enterotype with increased abundance of B. cellulosilyticus, which is linked to weight
gain, increased cholesterol synthesis, and is inversely correlated with specific arabinoxylan-degrading clades of Prevotella (copri).

In summary, the work presented in this PhD supports a link between microbial enterotypes and body weight, when a diet rich in whole grain fibers is consumed. However, the results also underline that future studies should explore enterotypes beyond genus level and include relevant host genes (i.e.
AMY1) in combination with microbial metabolites (i.e. SCFA) in comprehensive multi omics analyses to fully entangle the interactions between enterotype-related species, dietary fiber, and host metabolism.