Circadian orchestration of host and gut microbiota in infection

Abstract

Circadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS‐CoV‐2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota‐targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.

Gut microbiota bridges dietary nutrients and host immunity

“…For example, some certain AAs that are not involved in protein synthesis (e.g., γ-aminobutyric acid (GABA)) orchestrate immune cell fates (including macrophages, T cells, and B cells) (Liao et al, 2022;Ren et al, 2019;Xia et al, 2021b) and/or intestinal epithelial cell homeostasis (Xia et al, 2019), and there exists a crosstalk between GABA and intestinal microbiota (Strandwitz et al, 2019); nevertheless, whether and how gut microbiota mediates the roles of GABA in directing host immunity is unknown. Moreover, the main Trp-associating metabolitemelatonin is well demonstrated to affect immune cell functions (Du et al, 2022;Xia et al, 2022); however, only little attention has been paid to the interaction of melatonin and gut microbiota in dictating host immunity as well as the inflammatory diseases (Liu et al, 2020c;Xia et al, 2023;Zhai et al, 2021). Notably, given the complex interactions between the AAs and gut microbiota, multi-omics methods, for example, spatial-omics (transcriptomics, proteomics, and metabolomics), may be essential tools to improve our understanding of the AAs and gut microbiota in determining host health and immune-mediated diseases.…”

Circadian rhythms of hosts and their gut microbiomes: Implications for animal physiology and ecology

“…Yet, gut microbial oscillations themselves are a crucial component in the downstream synchronisation of multiple circadian phenotypes post‐feeding. Whilst numerous molecules, microbial metabolites and bacterial proteins are involved in signalling pathways that mediate circadian rhythms in immunity, metabolism, and behaviour (reviewed in Choi et al, 2021; Teichman et al, 2020; Xia et al, 2022), we focus on two components of the immune system (antimicrobial peptides and secretory Immunoglobulin A) most thoroughly studied in the context of bacterial circadian rhythms and pathogen defence (Figure 2). The roles of gut bacteria in this crosstalk can be separated by gut biogeography: bacteria that colonise the mucosal gut lining, termed mucosal commensal s; and bacteria that are mostly found in the gut lumen, termed luminal bacteria (Van den Abbeele et al, 2011).…”

“…The role of the gut microbiota in the regulation of circadian phenotypes has important implications for our understanding of diverse biological and ecological processes. For instance, the disruption of microbial oscillations is linked to organismal senescence (Paschos & FitzGerald, 2017), increased infection susceptibility (Xia et al, 2022), and metabolic disorders (Choi et al, 2021; Reitmeier et al, 2020), possibly via the dysregulation of circadian gene expression (Leone et al, 2015; Thaiss et al, 2016). These findings raise the possibility that gut microbial dysbiosis may be characterised by a lack of rhythmicity in the gut microbiome (e.g.…”

Melatonin in food allergy: Mechanism and potential therapy

“…The composition of gut microbiota in children with food allergies is significantly different from the healthy children 175,176 ; and germ-free mice do not develop food allergies. 177 Considering that melatonin functions in regulating many pathophysiological events through remodeling gut microbiota, 107,[178][179][180] future investigations are in need to determine whether and how melatonin suppresses food allergies through gut microbiota. Sensitization to allergens and the initiation of allergic diseases begin at epithelial barriers, including the gut, skin, and lungs.…”