Humans’ indigenous microbes strongly influence organ functions in an age‐ and diet‐dependent manner, adding an important dimension to aging biology that remains poorly understood. Although age‐related differences in the gut microbiota composition correlate with age‐related loss of organ function and diseases, including inflammation and frailty, variation exists among the elderly, especially centenarians and people living in areas of extreme longevity. Studies using short‐lived as well as nonsenescent model organisms provide surprising functional insights into factors affecting aging and implicate attenuating effects (...) of microbes as well as a crucial role for certain transcription factors like forkhead box O. The unexpected beneficial effects of microbes on aged animals imply an even more complex interplay between the gut microbiome and the host. The microbiome constitutes the major interface between humans and the environment, is influenced by biosocial stressors and behaviors, and mediates effects on health and aging processes, while being moderated by sex and developmental stages. (shrink)

Human evolution has been punctuated by climate anomalies, structuring environments, deadly infections, and altering landscapes. How well humans adapted to these new circumstances had direct effects on fitness and survival. Here, how the gut microbiome could have contributed to human evolutionary success through contributions to host nutritional buffering and infectious disease resistance is reviewed. How changes in human genetics, diet, disease exposure, and social environments almost certainly altered microbial community composition is also explored. Emerging research points to the microbiome as (...) a key player in host responses to environmental change. Therefore, the reciprocal interactions between humans and their microbes are likely to have shaped human patterns of local adaptation throughout our shared evolutionary history. Recent alterations in human lifestyle, however, are altering human microbiomes in unprecedented ways. The consequences of interrupted host–microbe relationships for human adaptive potential in the future are unknown. (shrink)