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Microbes are everywhere around us, including the inside of our own body. The human intestinal tract is colonized by an extremely complex microbial ecosystem. The microbial communities that are part of this ecosystem are very well adapted to our intestinal tract, and have developed close (often symbiotic) interactions with it. Some examples of their functions include fermenting unused energy substrates, producing vitamins for the host and protecting the host against intestinal pathogens. Therefore, it is assumed that the health of a host is influenced by the maintenance and restoration of his or her microbiota.
Intestinal microbiota is extremely diverse, mainly caused by the range of processes their involved in, the complexity of their interactions and the number of trophic levels they inhabit. However, it is important to characterize the composition and function of this intestinal microbiota in different environments, because it may give us insight how these aspects are related to the health status of the host. Therefore, researchers have been trying to unravel the ins and outs of our microbiota over the past few years.
State of the art
The early stages of human development occur in an environment free of microorganisms, so their gastrointestinal tract is not colonized yet at birth. However, after birth the baby comes in contact with all kinds of microorganisms, i.e. through its mother or caretakers. Because milk neutralises the stomach of a baby, the microbes are able to enter and colonize the gastrointestinal tract in a progressive way.
The region-specific colonization is related to the food retention time in the different parts of the digestive tract. For example, colonization of the stomach and small intestines is limited due to a short retention time, whereas the lower digestive tract is densely populated by microorganisms. The latter is caused by long term interactions with the microbiota. For example, some microorganisms use the mucous lining of the colon as an important carbon and energy source. Therefore, these microorganisms do not have to compete with microbiota inhabiting the lumen, and do not depend on host food consumption. They thus continually degrade the mucus layer which is replaced by a new one, creating some sort of a recycling mechanism.
However, due to processes of colonization, recolonization and suppression, it takes a few years before the microbial ecosystem gets into a stable state. When this happens, every individual has its own unique microbiota composition, driven by environmental and genetic influences. Each biome composition performs similar functions, although these may be performed by different phylotypes. However, researchers noticed that although infinite different ecosystems are possible, there were some 'common cores': three distinct microbe network types that were found across all global populations, and which were driven by certain groups of intestinal taxa. These three clusters of microorganisms are also known as enterotypes, and are relatively stable communities over a lifetime. Recent findings suggest that enterotypes are associated with energy and metabolic homeostasis of the host, which may in turn affect health and disease status.
Therefore, many researchers are interested in the composition and function of intestinal microbiota in relation with diseases, because this may provide us with potential biomarkers. Unfortunately, we cannot culture and study microorganisms from the gut, because a lot of them are anaerobic organisms. Therefore, faecal sampling are performed to study their genomic 'signatures'. To study the microbial community structure and the functional potential of different strains, researchers have performed comparative sequence analyses of highly conserved genes (such as rRNA). However, this is not really reliable, because it is not known if and how the certain genes are transcribed or expressed. Furthermore, the DNA could originate from dormant or even dead cells. Therefore, they found that it would be better to directly probe messenger RNA or proteins in future research, because this will also provide information on the function of gut microbes.
Many research has been performed to identify the biomarkers for obesity, because the intestinal microbiota are suggested to be of great importance in human energy balance and weight control. However, research comparing random humans with high and low BMIs with respect to their microbiota showed conflicting results, probably due to the fact that the subjects are often highly heterogeneous in their genotype, lifestyle and the specificity of their microbiota. Therefore, in more recent research, monozygotic twins were used to decrease the genotypic influences on the host phenotype.
To find some potential biomarkers for BMI differences (independent of genotype and absolute BMI values), monozygotic twins which were discordant for BMI were compared to see if there is a difference in certain functional groups of microbiota. It was found that twins overall have a highly similar microbiota (both in concordant and discordant pairs, compared to randomly paired subjects). To determine which microbial groups determined this high similarity, similarity indices between all subjects were calculated for all microbial subgroups. This showed that the structural core is strongly determined by genetics and possibly also influenced by shared early life environmental exposures. Therefore, the similarities can be seen as 'imprinted structural cores'.
To evaluate if and which microbial groups are associated with BMI differences, the microbiota composition of twins with discordant BMIs were compared to twins with concordant BMIs. It was found that siblings with a lower BMI had a microbial network that is specialized in the degradation of complex fibers, whereas the higher BMI siblings seemed to have a more butyrate producing network. This was also confirmed by examining the fermentation products of both groups. This suggests that a shift in fermentation pattern can be related to energy harvest potential, thus affecting BMI.
Another research concerning human health investigates the extreme diet case, where they measured the effect of following a very low calorie diet on the abundance and distribution of gut microbiota. It was shown that in test subjects which followed the diet, bacteria from the genus Akkermansia were more abundant. This was explained by the fact that these organisms are able to degrade mucus, which gives them a competitive advantage during nutrient deficiency (because they are independent of food consumption by the host). Further research showed that these organisms, which are part of two of the tree enterotypes, are true symbionts of humans. For example, some strains are able to produce short fatty acids which are easily taken up by the host. Furthermore, they can produce propionate, a compound which can cause immune stimulation and metabolic signalling. And last, they can contribute to a healty microbiota composition, for they are able to help in re-establishing the microbiota after severe environmental disturbances. Therefore, the presence of Akkermansia spp. gives an insight on gut health.
Discussion and future developments
The last section addresses points of discussion (strengths or weaknesses), puts the recent
findings in a broader perspective, addresses gaps in our knowledge and contains
suggestions for future research.