What are the consequences of the disappearing human microbiota?

Abstract

Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.

Figure 1 |. The effect of maternal status on the resident microbiota of the next generation.

We propose that, since the earliest days of the evolution of mammals, there has been major maternal transmission of microbiota to their offspring (vertical transmission). However, loss of the conserved microbiota in one generation leads to its loss in the next. For humans, until recently, horizontal microbial transmission also occurred and could compensate for the loss of vertical transmission. Members of the microbiota were horizontally transmitted through faecally contaminated drinking and bathing water, and high physical contact as a result of social crowding and large families; in many modern societies, these routes have diminished. The progressive loss of vertically transmitted microorganisms without horizontal replacement represents a cumulative birth cohort phenomenon.

Figure 2 |. Helicobacter pylori prevalence in the United States by age and year of birth.

Helicobacter pylori prevalence in males (a) and females (b) was determined in two large national studies (the National Health and Nutrition survey (NHANEs) III and NHANEs Iv), which were conducted in 1988–1991 and 1999–2000, respectively. These data, involving 15,000 subjects, are consistent with a now well-recognized birth cohort effect^– in which H. pylori acquisition, and thus prevalence, has been declining in industrialized countries for >100 years. The numbers next to each point represent the midpoint year of birth for each group of survey subjects (with each group covering one decade of births). Image is modified, with permission, from REF. © (2008) University of chicago Press.

Figure 3 |. interactions between host and microbiota.

a | For luminal microbiota that do not interact with host cells, the host-specific regulatory networks are essentially unaffected by transient microbiota or by luminal microbiota that are distant from the epithelium. This could represent a large class of organisms in the microbiota. b | For microbiota that interact with epithelial cells, there is an equilibrium relationship involving signalling between the microbial populations and the host. c | For co-evolved microbiota that interact with multiple cell types, the cross-signalling in the most fully co-evolved states involves multiple host cell types, including epithelial, immunological and neuroendocrine cells. The interaction of Helicobacter pylori with the gastric mucosa is representative of this model. The introduction of drugs, such as the commonly used proton pump inhibitors that reduce gastric acidity, affects equilibrium values and selects for a differing microbiota^,. d | In the absence of a microbiota, the indigenous host regulatory mechanisms predominate and reach different homeostasis values than are reached when interacting microbiota are present. In the situation of a disappearing microbiome, a and d predominate.