Abstract
Insulin resistance is a hallmark of Alzheimer's disease (AD), type II diabetes (T2D), and Parkinson's disease (PD). Emerging evidence indicates that these disorders are typically characterized by alterations in the gut microbiota composition, diversity, and their metabolites. Currently, it is understood that environmental hazards including ionizing radiation, toxic heavy metals, pesticides, particle matter, and polycyclic aromatic hydrocarbons are capable of interacting with gut microbiota and have a non-beneficial health effect. Based on the current study, we propose the hypothesis of "gut microenvironment baseline drift". According to this "baseline drift" theory, gut microbiota is a temporarily combined cluster of species sharing the same environmental stresses for a short period, which would change quickly under the influence of different environmental factors. This indicates that the microbial species in the gut do not have a long-term relationship; any split, division, or recombination may occur in different environments. Nonetheless, the "baseline drift" theory considers the critical role of the response of the whole gut microbiome. Undoubtedly, this hypothesis implies that the gut microbiota response is not merely a "cross junction" switch; in contrast, the human health or disease is a result of a rich palette of gut-microbiota-driven multiple-pathway responses. In summary, environmental factors, including hazardous and normal factors, are critical to the biological impact of the gut microbiota responses and the dual effect of the gut microbiota on the regulation of biological functions. Novel appreciation of the role of gut microbiota and environmental hazards in the insulin resistance would shed new light on insulin resistance and also promote the development of new research direction and new overcoming strategies for patients.