Famed microbiologist René J. Dubos (1901-1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He recognized the co-evolutionary relationship between microbiota and the human host. Almost 2 decades before the hygiene hypothesis, he suggested that children in developed nations were becoming too sanitized (vs. our ancestral past) and that scientists should determine whether the childhood environment should be "dirtied up in a controlled manner." He also argued that oft-celebrated growth chart increases via changes in the global food supply and dietary patterns should not be equated to quality of life and mental health. Here in the second part of our review, we reflect the words of Dubos off contemporary research findings in the areas of diet, the gut-brain-axis (microbiota and anxiety and depression) and microbial ecology. Finally, we argue, as Dubos did 40 years ago, that researchers should more closely examine the relevancy of silo-sequestered, reductionist findings in the larger picture of human quality of life. In the context of global climate change and the epidemiological transition, an allergy epidemic and psychosocial stress, our review suggests that discussions of natural environments, urbanization, biodiversity, microbiota, nutrition, and mental health, are often one in the same.