A diet that is as diverse as possible is important to maintain a healthy, diverse gut microbiome that supports metabolic health.
Both obesity and type 2 diabetes are multifactorial diseases and are based on a close interaction of genetic predisposition and a number of environmental influences. Diet plays a central role as an “environmental factor” in the development of these diseases. In recent years, it has become apparent that an unbalanced diet can not only lead to the intake of excess calories, but also have a dramatic impact on the microorganisms that colonize the human gastrointestinal tract.
Through a systematic study of the gut microbiome – the totality of microorganisms living in the gut – using DNA sequencing and bioinformatics methods, a large number of studies have now established the close link between alterations in the gut microbiota and the development of a wide variety of diseases; including obesity and type 2 diabetes. The gut microbiota represents a complex ecosystem consisting of a large number of mainly bacteria, but also archaea and viruses, with a mass of about 1.5 kg and an enormous diversity.
Challenges for functional understanding
To date, more than 1 000 bacterial species have been described, of which only circa 160 form a core microbiome recognizable between individuals. The combined genome of these more than 1 000 microbiota exceeds the human genome by about 100-fold. This high diversity and complexity of the microbiome and the fact that only a fraction of the microbiota can be cultured outside the body remain one of the greatest challenges to a functional understanding of the gut microbiome. Nevertheless, several clinical studies, both in obesity and type 2 diabetes, have succeeded in identifying specific signatures of the microbiota or its metabolites, which can at least provide the basis for further functional analyses. It should be noted, however, that the composition of the microbiome between individuals is highly dependent on age, gender, and ethnicity, making it significantly more difficult to extrapolate these study results to a broad population.
Gut microbiota have potential to regulate body weight
Studies in germ-free mice showed that in the absence of intestinal microbiota, there is less weight gain compared to mice conventionally colonized with bacteria when these mice are fed high-fat diets. Based on this, intestinal microbiota from twins that differed in obesity were transplanted into germ-free mice. Even when fed a diet rich in plant components and low in fat, mice receiving microbiota from obese twins gained more weight than mice receiving microbiota from lean twins. This demonstrated that changes in gut microbiota are not only the consequence of obesity, but conversely are also significantly involved in the regulation of weight gain.
Nevertheless, the applicability of these experiments to humans must be viewed with caution, as the same study also showed that socialization of mice with “fat” and “thin” microbiota resulted in the “fat” mice adopting microbiota from the “thin,” thus increasing the diversity of their microbiota and gaining less weight. This suggests that, in principle, the gut microbiota has the potential to regulate body weight, but the actual effects are highly dependent on complex environmental conditions.
In principle, it has been established that diversity of the microbiota is of great importance for a “healthy” gut microbiome, and that changes in individual bacterial species do not necessarily occur, but rather shifts in the ratios of bacterial strains to each other occur together with pathological changes.
For example, weight gain is very strongly associated with an increased incidence of Firmicutes compared with Bacteroides, which together comprise about 90 percent of known bacterial species. Functionally, this is in turn reflected in a shift in the production of short-chain fatty acids, with increased production of propionate in obese subjects and a predominance of butyrate in lean subjects. Furthermore, a large number of studies have identified individual bacterial species that correlate with different factors, such as body weight, blood glucose but also different inflammatory parameters, including for example Akkermansia muciniphila, Lactobacillus gasseri and Faecalibbacterium prausnitzii.
However, interpretation of these results is complicated because individual bacterial species must not be considered in isolation but always as part of an ecosystem in which changes in one bacterial species alter the entire ecosystem, thereby affecting the abundance of other bacterial species. For this reason, the concept of enterotypes was introduced, which should be understood as groups of bacteria that correlate together with defined metabolic phenotypes, or directly influence them.
Functional network instead of phylogenetic tree
This new approach is useful because of the increasing number of genome sequencing data of different microbiomes, as the focus here is no longer on taxonomic classification into bacterial species, strains, etc., but rather on functional grouping based on shared or complementary gene functions. This approach, which is gaining in popularity, thus focuses on a functional network instead of a phylogenetic tree.
Regardless of this approach, a diverse gut microbiome can positively influence the metabolic health of the host and thus represents an attractive therapeutic approach in metabolic syndrome.
Initial colonization of the gut occurs during birth by maternal bacteria and reaches a stable equilibrium from about 3 years of age (11, 12). In old age, the stability of the microbiome decreases again due to medication and other environmental factors.
Normal colonization of the intestine, but also of the skin and oral cavity, occurs during and after birth by vaginal microbiota of the mother and differs in the case of birth by sectio, because here colonization occurs mainly by maternal skin bacteria, resulting in a reduced diversity of the initial microbiome. Interestingly, this reduced diversity is associated with an increased risk of developing obesity.
However, the exact reasons for this association with morbid obesity, which occurs much later in the children’s lives, have not yet been adequately explored. However, in a recent study, it was shown that exposure of infants born by sectio to vaginal fluid from the mother was sufficient to establish a microbiome similar to that of infants born vaginally. Accordingly, it will be very informative to see if this exposure has long-term beneficial consequences.
In addition to the mode of birth, factors such as infant genetics, breastfeeding versus bottle feeding, and antibiotic use also play an important role in the initial development of gut microbiome diversity. Furthermore, the type of diet not only affects the composition of the microbiome during the first years of life, but also exerts continuous, strong selection pressure on gut bacteria throughout life. A dietary change in adults can lead to measurable changes in the gut microbiota within three days, which are reversible in the short term.
However, if certain nutrients or dietary fiber are not consumed for a prolonged period of time, nonreversible changes in the gut microbiota will occur. For this reason, it should also be considered that the reduction of sugars and starches in the treatment of diabetics should possibly be accompanied by the addition of indigestible carbohydrates to counteract a reduction in microbial diversity.
In general, diversity of the gut microbiota is higher in vegetarians than in mixed dieters-although avoidance of animal nutrients may also lead to selective reduction of individual microbiota. Regardless of diet type, there has been a sharp reduction in food diversity over the past 50 years, which interestingly correlates with the sharp increase and obesity and type 2 diabetes. Thus, a diet that is as diverse as possible is also important for maintaining a healthy, diverse gut microbiome that supports metabolic health.
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