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.
Highlights
Insulin resistance, a medical status in which the insulin production is sufficient but the body is failing to make use of insulin properly, is a hallmark of Alzheimer’s disease (AD), type II diabetes (T2D), and Parkinson’s disease (PD) (Cardoso and Moreira, 2020; Xi and Xu, 2021)
The gut microbiota has captured the attention of biologists, physicians, and the public
With increasing in-depth studies, detailed understanding of the gut microbiota has provided us important insights into the molecular mechanisms underlying insulin-related regulation
Summary
A medical status in which the insulin production is sufficient but the body is failing to make use of insulin properly, is a hallmark of Alzheimer’s disease (AD), type II diabetes (T2D), and Parkinson’s disease (PD) (Cardoso and Moreira, 2020; Xi and Xu, 2021). Chiu et al reviewed the impact of environmental chemicals on gut microbiota and suggested that pesticide exploration contributes to alterations in the composition, gene expression, function, and health effects in the host, including metabolism, immunity, and neurological function (Chiu et al, 2020) These studies reinforce the notion that the gut microbiota response has the property of baseline drift. Studies involving a larger sample population and those elucidating the relative molecular mechanisms should be conducted to improve clinical outcomes and address challenges regarding accessibility, acceptability, lack of standardization, and regulatory complexity of fecal transplantation (Fadda, 2020) Another targeting strategy to prevent insulin resistance is the use of probiotics (Alard et al, 2016). While the mechanistic basis of therapeutic efficacy and safety is critical for mining new targets and signaling pathways for intervention, further appreciation of the baseline drift of gut microbiota biology will be required for successful clinical applications
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