Microbes Inside: From Structure to Function

Since early life, microbes dominate our body in numbers. In the intestinal tract they constitute the largest microbial ecosystem that is close to our heart: our microbes inside. Since most of these are exclusively found in the human intestine and we are born virtually sterile, it is likely that colonization of the newborn is a large fecal transplantation that has been shown to involve maternal transfer. While serial colonization of different microbes has been assumed, we have recently observed that the inoculation of healthy babies may be occurring in a short window of opportunity and involves sequential outgrowth, programmed by substrates and antimicrobial proteins made by baby and mother. This delicate process has great impact on the babies’ development and later life health as we have shown in colic babies. Moreover, various factors jeopardize this development and we found that multiple use of specific antibiotics have pervasive effects on the intestinal microbiota and is associated with development of asthma-related symptoms several years later. Previous molecular studies have shown that the intestinal tract microbiota is highly personalized. We now have confirmed and extended this in comparative studies with close to 10,000 subjects that show all a different microbial composition. However, we could detect a conserved core network of functionally related microbes, high-level enterotype-like structures, and specific abundance distributions in healthy Western adults. The latter provides support for the presence of alternative stable states with bistable groups reflecting tipping elements. We propose that these states are instrumental for further defining microbiota aberrations that are now often designated with the misnomeric term dysbiosis. Moreover, these tipping points can be used to delineate early warning signals associated with health changes. Thus, considerable progress has been made in the understanding, the development and structure of our intestinal microbiota but we have only limited insight in their functions. High throughput RNAseq-based analysis has allowed a view of the functions in the upper intestinal tract while metaproteomics has shown to be instrumental in detecting colonic functions. However, while over 1000 microbial species have been cultured from the human intestine, several times more await culturing, the exact number depending on their definition. We have focused on commensal microbes involved in processes that are eminent in the human gut, such as the production of butyrate and propionate, not only from sugars but also from lactate and acetate, as well as mucus that is plentiful in the colon. These have been cultured, characterized at the genome level, and analyzed for their physiological properties and capacity to form trophic chains. In addition, some have been used in mouse models to study their impact on the host. The mucus-degrading Akkermansia muciniphila has been found to improve the intestinal barrier function in mice fed a high-fat diet and has recently been used in human trials to further characterize the host response.This contribution will address the recent developments in the structure and function of our microbes inside as summarized above. Moreover, attention will be given on how intestinal commensals can serve in next generation products to improve human health by targeting specific intestinal functions.