Host Demise as a Beneficial Function of Indigenous Microbiota in Human Hosts

Abstract

ABSTRACT The age structure of human populations is exceptional among animal species. Unlike with most species, human juvenility is extremely extended, and death is not coincident with the end of the reproductive period. We examine the age structure of early humans with models that reveal an extraordinary balance of human fertility and mortality. We hypothesize that the age structure of early humans was maintained by mechanisms incorporating the programmed death of senescent individuals, including by means of interactions with their indigenous microorganisms. First, before and during reproductive life, there was selection for microbes that preserve host function through regulation of energy homeostasis, promotion of fecundity, and defense against competing high-grade pathogens. Second, we hypothesize that after reproductive life, there was selection for organisms that contribute to host demise. While deleterious to the individual, the presence of such interplay may be salutary for the overall host population in terms of resource utilization, resistance to periodic diminutions in the food supply, and epidemics due to high-grade pathogens. We provide deterministic mathematical models based on age-structured populations that illustrate the dynamics of such relationships and explore the relevant parameter values within which population viability is maintained. We argue that the age structure of early humans was robust in its balance of the juvenile, reproductive-age, and senescent classes. These concepts are relevant to issues in modern human longevity, including inflammation-induced neoplasia and degenerative diseases of the elderly, which are a legacy of human evolution. IMPORTANCE The extended longevity of modern humans is a very recent societal artifact, although it is inherent in human evolution. The age structure of early humans was balanced by fertility and mortality, with an exceptionally prolonged juvenility. We examined the role of indigenous microbes in early humans as fundamental contributors to this age structure. We hypothesize that the human microbiome evolved mechanisms specific to the mortality of senescent individuals among early humans because their mortality contributed to the stability of the general population. The hypothesis that we present provides new bases for modern medical problems, such as inflammation-induced neoplasia and degenerative diseases of the elderly. We postulate that these mechanisms evolved because they contributed to the stability of early human populations, but their legacy is now a burden on human longevity in the changed modern world.