“Gut Microbiota-Circadian Clock Axis” in Deciphering the Mechanism Linking Early-Life Nutritional Environment and Abnormal Glucose Metabolism

Abstract

The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the “metabolic memory” and the Developmental Origins of Health and Disease (DOHaD) hypothesis. The mechanism of “metabolic memory” has become a hot topic in the field of DM worldwide and could be a key to understanding the pathogenesis of DM. In recent years, several large cohort studies have shown that shift workers have a higher risk of developing type 2 diabetes mellitus (T2DM) and worse control of blood glucose levels. Furthermore, a maternal high-fat diet could lead to metabolic disorders and abnormal expression of clock genes and clock-controlled genes in offspring. Thus, disorders of circadian rhythm might play a pivotal role in glucose metabolic disturbances, especially in terms of early adverse nutritional environments and the development of metabolic diseases in later life. In addition, as a peripheral clock, the gut microbiota has its own circadian rhythm that fluctuates with periodic feeding and has been widely recognized for its significant role in metabolism. In light of the important roles of the gut microbiota and circadian clock in metabolic health and their interconnected regulatory relationship, we propose that the “gut microbiota-circadian clock axis” might be a novel and crucial mechanism to decipher “metabolic memory.” The “gut microbiota-circadian clock axis” is expected to facilitate the future development of a novel target for the prevention and intervention of diabetes during the early stage of life.

WORKbiota: A Systematic Review about the Effects of Occupational Exposure on Microbiota and Workers’ Health

“…The composition of the gut microbiota is subject to diurnal variation and is entrained by host circadian rhythms. In turn, a diverse microbiota is essential for optimal regulation of host circadian pathways [68,72,73]. Additionally, significant relationships between nutrient intake and the circadian clock have been shown.…”

“…Additionally, significant relationships between nutrient intake and the circadian clock have been shown. Considering whether dysbiosis associated with sleep and circadian misalignment in shift workers affects clock genes in metabolic tissues will be important in future studies [68]. Only one narrative review searched for a link between exposure to occupational agents, changes in the microbiome, and possible development of health complications, in particular autoimmune disorders.…”

Early-life nutrition and metabolic disorders in later life: a new perspective on energy metabolism

“…What is the critical mechanism mediating the “metabolic memory”? Although emerging studies began to pay attention to the potential role of central hypothalamic regulation, [ 45 ] gut microbiota, [ 46 , 47 ] circadian rhythm, [ 48 , 49 ] and brown adipose tissue [ 50 , 51 ] in linking the early-life nutrition and metabolic health in later life, we mainly overviewed the evidence regarding the epigenetic regulation in this review. Sib-pairs study, one exposure to diabetes and the other to a non-diabetes in utero, indicated that metabolic programming was independent of genetic inheritance to some content.…”

The role of gut microbiota in infectious diseases

“…Individuals come into close contact with microorganisms, particularly the intestinal microbes that affects the development and maintenance of the immune system, after childbirth (may before; Gensollen et al, 2016; Mishra et al, 2021). The decreased diversity of the microbiota residing in the intestine, the largest human immune organ (Pan et al, 2020; Zhou et al, 2019), has been found in a variety of infectious diseases (Geng et al, 2020; Haak et al, 2018; Lv et al, 2019). These suggest that the impaired homeostasis of the intestinal microbiota may promote the development of infectious diseases, and the balance of intestinal microecology is essential for the prevention and control of infectious diseases.…”

“…. The decreased diversity of the microbiota residing in the intestine, the largest human immune organ (Pan et al, 2020;Zhou et al, 2019), has been found in a variety of infectious diseases (Geng et al, 2020;Haak et al, 2018;Lv et al, 2019). These suggest that the impaired homeostasis of the intestinal microbiota may promote the development of infectious diseases, and the balance of intestinal microecology is essential for the prevention and control of infectious diseases.…”