The circadian rhythm arises endogenously from genetically encoded molecular clocks, wherein the components collaborate to induce cyclic fluctuations, occurring approximately every 24 hours. The rhythms synchronize biological processes with regular and predictable environmental patterns to guarantee the host metabolism and energy homeostasis function and well-being. Disruptions to circadian rhythms are widely associated with metabolic disorders. Notably, microbial rhythms are influenced by both the host's intrinsic circadian clock and external rhythmic factors (i.e., light-dark cycle, diet patterns and diet composition), which affect the structure of microbial communities and metabolic functions. Moreover, microbiota and the metabolites also reciprocally influence host rhythms, potentially impacting host metabolic function. This review explores the bidirectional interactions between the circadian clock, factors influencing host-microbial circadian rhythms, and the effects on lipid metabolism and energy homeostasis. STATEMENT OF SIGNIFICANCE: This review explores the factors influencing both host and microbial rhythms, highlighting the interactions between gut microbiota, the metabolites, and host circadian rhythms. Additionally, it emphasizes the impact of disruptions in microbial and host rhythms on the development of metabolic diseases.

Theabrownin (TB), a prominent pigment in fermented dark tea, exhibits beneficial effects on adiposity reduction. Our study revealed that TB derived from Fu brick tea significantly lowered fasting blood glucose levels and insulin resistance in obese/diabetic KKAy mice. Furthermore, TB demonstrated potent anti-inflammatory effects in the liver, adipose tissue, and intestines, as well as enhancing intestinal integrity. Additionally, TB was found to inhibit hepatic gluconeogenesis and promote fatty acid oxidation. Notably, TB altered gut metabolites, particularly l-palmitoylcarnitine, which showed an elevation in serum, liver, and adipose tissue following TB intervention. l-Palmitoylcarnitine reduced gluconeogenesis in primary hepatocytes and decreased lipid deposition in both primary hepatocytes and 3T3-L1 adipocytes in vitro. However, these effects were abolished when the circadian gene Period 3 (Per3) was knocked down. Our findings suggest that l-palmitoylcarnitine may play a crucial role in improving TB-mediated glucose homeostasis and lipid metabolism by regulating Per3.

The last two decades have seen a major increase in our understanding of the role of the microbiome in health and disease. We now realise that these fellow travellers are really important regulators of various systems in the body across the lifespan. In this Special Issue, we bring together a collection of articles from leading authors who summarise the current state of the art of host-microbe interactions. While we celebrate the breakthroughs in microbiome science, we also acknowledge the challenges-variability in microbiota composition, the complexities of host-microbe interactions and the need for standardised methodologies. As research progresses, harnessing the power of the microbiome may pave the way for novel diagnostic and therapeutic strategies, reaffirming the notion that we are never alone-our microbial fellow travellers accompany us through life, for better or worse.

Microglia, the brain's resident macrophages, are key mediators of neuroinflammation, responding to immune pathogens and toxins. They play a crucial role in clearing cellular debris, regulating synaptic plasticity, and phagocytosing amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Recent studies indicate that microglia not only exhibit intrinsic circadian rhythms but are also regulated by circadian clock genes, influencing specific functions such as phagocytosis and the modulation of neuroinflammation. Disruption of the circadian rhythm is closely associated with AD pathology. In this review, we will provide an overview of how circadian rhythms regulate microglia-mediated neuroinflammation in the progression of AD, focusing on the pathway from the central nervous system (CNS) and the peripheral immune system. We also discuss potential therapeutic targets, including hormone modulation, lifestyle interventions, and anti-inflammatory therapies, aimed at maintaining brain health in AD. This will shed light on the involvement of circadian rhythm in AD and explore new avenues for AD treatment.

Obesity is associated with metabolic and immune perturbations (ie, insulin resistance, increased inflammation, and oxidative stress), circadian rhythm dysregulation, and gut microbial changes that can promote colorectal tumorigenesis. Colorectal cancer (CRC) is the third most incident cancer in the United States. This narrative review examines the effects of intermittend fasting on factors influencing colon tumorigenesis, such as body weight, metabolic and immune markers, circadian rythm, and the gut microbiota in humans. Findings suggest that intermittent fasting regimens can lead to weight loss and shifts in metabolic markers, which could be preventive for CRC but effects on the gut microbiota composition and functions still remains elusive.

This review aims to examine the effects of the photoperiod on farm animals and to provide insights into how lighting management can optimize production performance, reproduction, and welfare. The production performance of farm animals is influenced by a variety of factors, such as diet, breed, and environment. Among these, lighting is a crucial component of the feeding environment. With the advancement of intensive farming, lighting measures are increasingly receiving attention. The photoperiod regulates the biological rhythms of animals and affects the secretion of hormones within the animal's body, particularly melatonin. Melatonin regulates the secretion and release of several other hormones through various pathways, such as growth hormone, prolactin, and gonadotropins. Therefore, the environmental light cycle participates in a variety of physiological activities within animals. An appropriate photoperiod can enhance the production performance, reproduction performance, and welfare conditions of farm animals. Choosing the appropriate lighting duration based on different animals, physiological stages, and production purposes can enhance the economic benefits of farms. In this review, we summarized the recent findings on the impact of photoperiods in different farm animal feeding environments on animal husbandry, although research on the suitable photoperiod for some animals might be outdated and is also discussed in this article. For lactating dairy cows, calves, poultry, pigs (excluding boars), and rabbits, continuous light exposure exceeding 12 h per day can be implemented to enhance growth and production performance. In contrast, for boars and goats, daily light exposure should be limited to less than 10 h to optimize reproductive and productive efficiency. Overall, this review aimed to provide theoretical support for research on the optimal photoperiod for farm animals.

There is growing evidence that individuals with cardiovascular disease (CVD) are more likely to develop depression. The timing of food intake can significantly alter the body's circadian rhythm and affect the occurrence of depression. Currently, it is unknown whether and how energy or macronutrient intake times are associated with depression in adults with CVD.

To evaluate dietary energy or macronutrient intake (across three meals) associations with depression in adults with CVD in a nationally representative sample.

The study population consisted of 3,490 U.S. adults with CVD (including 554 with depression) from the National Health and Nutrition Examination Survey 2003-2018. Energy and macronutrient intake was measured by a 24-h dietary recall, and depression was diagnosed by the Patient Health Questionnaire (PHQ-9, score ≥ 10). According to dietary energy or macronutrient intake across three meals, adults with CVD were divided into five groups. Logistic regression analysis was performed to examine associations between energy or macronutrient intake and depression after adjusting for a series of confounding factors, including age, gender, education level, household income, smoking status, drinking status, physical activity, marital status, skipping breakfast/lunch/dinner, total energy, carbohydrate, protein, dietary fiber, SFA, MUFA, and PUFA intake, T2DM and hypertension status, and BMI. Dietary substitution models were used to explore changes in depression risk when 5% dietary energy intake at dinner or lunch was substituted with energy intake at breakfast.

When compared with participants in the lowest quintile of breakfast energy intake, those who received energy intake in the highest quintile at breakfast were associated with lower depression risk in those with CVD, and the adjusted odds ratio (OR) was 0.71 (95% CI, 0.51 to 0.91). When compared with participants in the lowest quintile of lunch or dinner energy intake, the risk of depression did not exhibit statistical significance when lunch or dinner energy intake was in the highest quintile, and the adjusted ORs were 1.08 (95% CI, 0.65 to 1.83) and 0.92 (95% CI, 0.62 to 1.37), respectively. Isocalorically replacing 5% of total energy at dinner or lunch with breakfast was associated with 5% (OR: 0.95, 95% CI 0.93 to 0.97) and 5% (OR: 0.95, 95% CI 0.93 to 0.96) lower risk of depression, respectively.

High energy intake at breakfast may be associated with a lower risk of depression in those with CVD. We should focus on the potential role of breakfast energy intake in preventing the onset of depression.

Chrononutrition, the study of the interaction between biological rhythms and nutrition, has emerged as a promising field for addressing metabolic health. However, its role in chronic kidney disease (CKD) remains underexplored. CKD patients often experience circadian disruptions due to renal, metabolic, treatment-related, and lifestyle factors, which may influence their nutritional status and clinical outcomes. Objective: to synthesize and analyze the existing evidence on chrononutrition in CKD patients, identify knowledge gaps, and propose directions for future research across different stages of CKD. Initially, this review contextualizes circadian physiology, alignment, and chronodisruption to explore such factors in CKD patients, focusing on chrononutrition variables already studied in the general population. We discuss how dietary timing and habit adjustments could influence CKD clinical outcomes, offering insights into circadian impacts on disease management. This new approach could optimize patient care, encouraging further research, particularly in the development of personalized strategies for different stages of the disease.

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

Tamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug. Here, using gnotobiotic- and antibiotics-treated mice, we show that tamoxifen pharmacokinetics are heavily influenced by gut bacteria and prolonged exposure to tamoxifen. Interestingly, 16S rRNA gene sequencing shows tamoxifen does not affect overall microbiota composition and abundance. Metabolomics, however, reveals differential metabolic profiles across the microbiomes of different donors cultured with tamoxifen, suggesting an enzymatic diversity within the gut microbiome that influences response to tamoxifen. Consistent with this notion, we found that β-glucuronidase (GUS) enzymes vary in their hydrolysis activity of glucuronidated tamoxifen metabolites across the gut microbiomes of people. Together, these findings highlight the importance of the gut microbiome in tamoxifen's pharmacokinetics.IMPORTANCEOne in eight women will develop breast cancer in their lifetime, and tamoxifen is used to suppress breast cancer recurrence, but nearly 50% of patients are not effectively treated with this drug. Given that tamoxifen is orally administered and, thus, reaches the intestine, this variable patient response to the drug is likely related to the gut microbiota composed of trillions of bacteria, which are remarkably different among individuals. This study aims to understand the impact of the gut microbiome on tamoxifen absorption, metabolism, and recycling. The significance of our research is in defining the role that gut microbes play in tamoxifen pharmacokinetics, thus paving the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.

The negative impact of repeated-mild traumatic brain injury (rmTBI) is profoundly seen in circadian-disrupted individuals. The unrelenting inflammation, glial activation, and gut dysbiosis are key neuropathological aberrations in the aftermath of rmTBI. In this study, we examined the impact of chitosan lactate (CL) on circadian disturbance (CD) + rmTBI-generated neurological dysfunctions and its prebiotic response on the gut-brain axis. Adult C57BL/6 mice were exposed to circadian disruption (CD) prior to rmTBI insults. The neurobehavioral changes were assessed by rotarod, open-field test (OFT), elevated zero maze (EZM), forced-swim test (FST), Y-maze, and novel object recognition test (NORT). The inflammatory, neuronal, and synaptic markers in the frontal cortex and hippocampus, and cecal gut microbiota phylum were examined using RT-PCR and western blotting. The goblet cells, tight junction proteins (occludin and zona occludens-1), and short-chain fatty acids (SCFAs) were analyzed using immunohistochemistry, alcian-blue PAS staining, and 1H-NMR methods. Mice exposed to CD + rmTBI (CDR) displayed robust neurological dysfunctions in rotarod, anxiety- and depressive-like behavior in EZM and FST, and cognition deficits in Y-maze and NORT. Administration of CL (1 and 3 mg/kg) mitigated the above neurobehavioral abnormalities. CL treatment also normalized the levels of inflammatory markers (NF-κB, IL-6, IL-18, and TNF-α), brain-derived neurotrophic factor, and neuronal/synaptic proteins (doublecortin, synaptophysin, and postsynaptic density protein-95). Increased goblet cells and tight junction proteins in the colon and SCFAs in the cecal samples indicated improved gut integrity following CL treatment. The results indicate that CL mitigated CDR-inflicted neurological abnormalities in mice by modulating neuroinflammation and gut-brain interactions.

Melatonin (MT) (N-acetyl-5-methoxytryptamine) is an indoleamine recognized primarily for its crucial role in regulating sleep through circadian rhythm modulation in humans and animals. Beyond its association with the pineal gland, it is synthesized in various tissues, functioning as a hormone, tissue factor, autocoid, paracoid, and antioxidant, impacting multiple organ systems, including the gut-brain axis. However, the mechanisms of extra-pineal MT production and its role in microbiota-host interactions remain less understood. This review provides a comprehensive overview of MT, including its production, actions sites, metabolic pathways, and implications for human health. The gastrointestinal tract is highlighted as an additional source of MT, with an examination of its effects on the intestinal microbiota. This review explores whether the microbiota contributes to MT in the intestine, its relationship to food intake, and the implications for human health. Due to its impacts on the intestinal microbiota, MT may be a valuable therapeutic agent for various dysbiosis-associated conditions. Moreover, due to its influence on intestinal MT levels, the microbiota may be a possible therapeutic target for treating health disorders related to circadian rhythm dysregulation.

Aging is an inevitable life process which is accelerated by lifestyle and environmental factors. It is an irreversible accretion of molecular and cellular damage associated with changes in the body composition and deterioration in physiological functions. Each cell (other than stem cells) reaches the limit of its ability to replicate, known as cellular or replicative senescence, and consequently, the organs lose their physiological functions, resulting in overall impairment. Other factors that promote aging include smoking, alcohol, UV rays, sleep habits, food, stress, sedentary lifestyle, and genetic abnormalities. These stress factors can alter our endogenous clock (the circadian rhythm) and the microbial commensals. As a result of the effect of these stressors, the microorganisms that generally support human physiological processes become baleful. The disturbance of natural physiology instigates many age-related pathologies, such as cardiovascular diseases, chronic obstructive pulmonary disorder, cerebrovascular diseases, opportunistic infections, high blood pressure, cancer, diabetes, kidney diseases, dementia, and Alzheimer's disease. The present review covers the three most essential processes of the circadian clock; the circadian gene mechanism and regulation, the mitotic clock (which plays a vital role in the telomere's attrition) and the gut microbiota and their metabolome that drive aging and lead to age-related pathologies. In conclusion, maintaining a synchronized circadian rhythm, a healthy gut microbiome, and telomere integrity is essential for mitigating the effects of aging and promoting longevity. The interplay among these factors underscores the importance of lifestyle choices in enhancing overall health and lifespan.

Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host-microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation.

Gut flora is considered to modulate lipid transport from the intestine into the bloodstream, and thus may potentially participate in the development of GDM. Although previous studies have shown that the intestinal microbiota influences lipid transport and metabolism in GDM, the precise mechanisms remain elusive. To address this, we used a high-fat diet (HFD)-induced GDM mouse model and conducted 16s rRNA sequencing and fecal metabolomics to assess gut microbial community shifts and associated metabolite changes. Western blot, ELISA, and chromatin immunoprecipitation (ChIP) were utilized to elucidate how gut microbiota affect intestinal lipid transport and the insulin sensitivity of hepatic, adipose, and skeletal muscle tissues. We found that HFD impaired the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in pregnant mice. 16s rRNA sequencing demonstrated profound compositional changes, especially in the relative abundances of Firmicutes and Bacteroidetes. Metabolomics analysis presented a decline in the concentration of short-chain fatty acids (SCFAs) in the GDM group. Western blot analyses showed an upregulation of HDAC3 and a concurrent reduction in H3K27 acetylation in the intestine. ChIP-qPCR showed that PPAR-γ was inhibited, which in turn activated lipid-transporter CD36. ELISA and insulin signaling pathway detection in insulin-target organs showed high concentrations of circulating fatty acids and triglycerides and insulin resistance in insulin-target organs. Our results suggest that gut microbiota is closely associated with the development of GDM, partly because decreased gut flora-associated SCFAs activate CD36 by suppressing the HDAC3-H3K27ac-PPAR-γ axis to transport excessive fatty acids and triglycerides into blood circulation, thereby dysregulating the insulin sensitivity of insulin target organs.

Introduction. Alcohol dependence (AD) and sleep disturbance (SD) independently affect gut microbiota, potentially disrupting the circadian rhythm of the microbiota and the host. However, the impact of SD on the composition and rhythmicity of gut flora in AD patients remains poorly understood.Gap Statement. Characteristics of gut flora and diurnal oscillations in AD patients experiencing SD are unknown.Aim. This study aims to explore alterations in gut flora and diurnal oscillations in AD patients experiencing SD.Methodology. Thirty-two AD patients and 20 healthy subjects participated, providing faecal samples at 7 : 00 AM, 11 : 00 AM, 3 : 00 PM and 7 : 00 PM for gut microbiota analysis using 16S rDNA sequencing. AD patients were further categorized into those with poor sleep (ADwPS) and those with good sleep (ADwGS) for further analyses.Results. The ADwPS group demonstrated elevated levels of anxiety, depression and withdrawal severity compared to the ADwGS group (all P<0.05). The β-diversity of gut microbiota in the ADwPS group differed from that in the ADwGS group (P<0.05). Bacterial abundances at various taxonomic levels, including Cyanobacteria and Pseudomonadales, differed between the ADwPS and ADwGS groups (all P<0.05). Utilizing unweighted UniFrac analysis, the β-diversity of gut microbiota in the ADwPS group demonstrated robust diurnal oscillation (P<0.05), whereas this pattern was statistically insignificant in the ADwGS group. Notably, the abundance of pathogenic bacteria like Pseudomonadales and Pseudomonadaceae exhibited marked diurnal fluctuation in the ADwPS group (all P<0.05).Conclusion. SD in AD patients extends beyond alcohol-induced alterations, impacting gut microbiota composition, function and diurnal oscillation patterns. This highlights its add-on influence, supplementing AD-related changes.

Chronotypes play a crucial role in regulating sleep-wake cycles and overall health. The aim of this study was to investigate chronotype, sleep quality, polymorphisms of clock genes and the level of leptin in serum. We used standardized questionnaires to assess chronotype and sleep quality. Genetic analysis was performed to determine the selected clock gene polymorphism. Serum leptin level was measured by the Elisa method. The results showed that serum leptin concentration was elevated in women, as well as in men who had a high waist-to-hip ratio (WHR) and body mass index (BMI). The evidence indicated that younger students (<22 years old) were most likely to experience poor sleep quality. Nevertheless, our multivariate analysis revealed that young age and a morning-oriented chronotype were associated with better sleep quality. We noted that clock gene polymorphisms were present in 28.6% of the participants. Moreover, polymorphisms of PER1 c.2247C>T (rs2735611) and PER2 c.-12C>G (rs2304672) genes were associated with serum leptin level and chronotype, respectively. These findings provide insights into the relationships between chronotype, sleep quality, clock gene polymorphisms and obesity risk in biomedical students. Understanding these factors can contribute to better sleep management and potential interventions to improve health outcomes in humans.

Diet is a robust entrainment cue that regulates diurnal rhythms of the gut microbiome. We and others have shown that disruption of the circadian clock drives the progression of colorectal cancer (CRC). While certain bacterial species have been suggested to play driver roles in CRC, it is unknown whether the intestinal clock impinges on the microbiome to accelerate CRC pathogenesis. To address this, genetic disruption of the circadian clock, in an Apc-driven mouse model of CRC, was used to define the impact on the gut microbiome. When clock disruption is combined with CRC, metagenomic sequencing identified dysregulation of many bacterial genera including Bacteroides, Helicobacter, and Megasphaera. We identify functional changes to microbial pathways including dysregulated nucleic acid, amino acid, and carbohydrate metabolism, as well as disruption of intestinal barrier function. Our findings suggest that clock disruption impinges on microbiota composition and intestinal permeability that may contribute to CRC pathogenesis.

Dietary components, including dietary fiber, unsaturated fatty acids, and polyphenols, along with meal timing and spacing, significantly affect the microbiota's capacity to produce various metabolites essential for quality sleep and overall health. This review explores the role of gut microbiota in regulating sleep through various metabolites such as short-chain fatty acids, tryptophan, serotonin, melatonin, and gamma-aminobutyric acid. A balanced diet rich in plant-based foods enhances the production of these sleep-regulating metabolites, potentially benefiting overall health. This review aims to investigate how dietary habits affect gut microbiota composition, the metabolites it produces, and the subsequent impact on sleep quality and related health conditions.

The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.

Microbiomes are ecosystems, and their stability can impact the health of their hosts. Theory predicts that predators influence ecosystem stability. Phages are key predators of bacteria in microbiomes, but phages are unusual predators because many have lysogenic life cycles. It has been hypothesized that lysogeny can destabilize microbiomes, but lysogeny has no direct analog in classical ecological theory, and no formal theory exists. We studied the stability of computationally simulated microbiomes with different numbers of temperate (lysogenic) and virulent (obligate lytic) phage species. Bacterial populations were more likely to fluctuate over time when there were more temperate phages species. After disturbances, bacterial populations returned to their pre-disturbance densities more slowly when there were more temperate phage species, but cycles engendered by disturbances dampened more slowly when there were more virulent phage species. Our work offers the first formal theory linking lysogeny to microbiome stability.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation.

The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

Chronic consumption of a high-calorie diet coupled with an altered sleep-wake cycle causes disruption of circadian clock that can impact the gut microbiome leading to metabolic syndrome and associated diseases. Herein, we investigate the effects of a high fat high fructose diet (H) alone or in combination with photoperiodic shifts induced chronodisruption (CD) on gut microbiota of C57BL/6J male mice. Further, the merits of daily evening intraperitoneal administration of melatonin in restoring gut microbiota are studied herein. Experimental groups viz. H, CD and HCD mice recorded higher levels of serum pro-inflammatory cytokines (TNF-α and IL-6) and lower levels of the anti-inflammatory cytokine, IL-10. These findings correlate with a concomitant increase in the transcripts of TLR4, TNF-α, and IL-6 in small intestine of the said groups. A decrement in mRNA levels of Ocln, ZO-1 and Vdr in these groups implied towards an altered gut permeability. These results were in agreement with the observed decrement in percentage abundance of total gut microflora and Firmicutes: Bacteroidetes (F/B) ratio. Melatonin administration accounted for lower-level inflammation (serum and gut) along with an improvement in gut permeability markers. The total abundance of gut microflora and F/B ratio showed an improvement in all the melatonin-treated groups and the same is the highlight of this study. Taken together, our study is the first to report perturbations in gut microbiota resulting due to a combination of photoperiodic shifts induced CD and a high fat high calorie diet-induced lifestyle disorder. Further, melatonin-mediated rejuvenation of gut microbiome provides prima facie evidence of its role in improving gut dysbiosis that needs a detailed scrutiny.

Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, a less restrictive diet that allows for cyclical periods of reduced calories mitigates aging phenotypes, yet the effects of such an intervention in a genetically heterogenous, higher-order mammal has not been examined. Here, using middle-aged rhesus macaques matched for age and sex, we show that a regimen of 4 days of low-calorie intake followed by 10 days of ad libitum feeding (4:10 diet) performed in repeating cycles over 12 weeks led to significant loss of weight and fat percentage, despite the free access to food for most of the study duration. We show the 4-day restriction period is sufficient to drive alterations to the serum metabolome characterized by substantial differences in lipid classes. These phenotypes were paralleled by changes in the gut microbiome of restricted monkeys that highlight the involvement of a microbiome-metabolome axis. This regimen shows promising phenotypes, with some sex-dimorphic responses, including residual memory of the diet. As many calorie restriction interventions are difficult to sustain, we propose that this short-term diet may be easier to adhere to and have benefits directly relevant to human aging.

Retinal thickness is related to Parkinson's disease (PD), but its association with the severity of PD is still unclear. We conducted a Mendelian randomized (MR) study to explore the association between retinal thickness and PD. For the two-sample MR analysis, the summary statistics obtained from genome-wide association studies on the thickness of Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) were employed as exposure, while the summary statistics associated with PD were used as the outcome. The primary approach utilized was inverse variance weighted. To correct for multiple testing, the false discovery rate (FDR) was employed. For sensitivity analysis, an array of robust MR methods was utilized. We found genetically predicted significant association between reduced RNFL thickness and a reduced risk of constipation in PD (odds ratio [OR] = 0.854, 95% confidence interval [CI] (0.782, 0.933), P < 0.001, FDR-corrected P = 0.018). Genetically predicted reduced RNFL thickness was associated with a reduced Unified Parkinson's Disease Rating Scale total score (β = -0.042, 95% CI (-0.079, 0.005), P = 0.025), and reduced GCIPL thickness was associated with a lower risk of constipation (OR = 0.901, 95% CI (0.821, 0.988), P = 0.027) but a higher risk of depression (OR = 1.103, 95% CI (1.016, 1.198), P = 0.020), insomnia (OR = 1.090, 95% CI (1.013, 1.172), P = 0.021), and rapid eye movement sleep behaviour disorder (RBD) (OR = 1.198, 95% CI (1.061, 1.352), P = 0.003). In conclusion, we identify an association between retinal thickness and non-motor symptoms (constipation, depression, insomnia and RBD) in PD, highlighting the potential of retinal thickness as a biomarker for PD nonmotor symptoms.

Circadian rhythms influence various aspects of the biology and physiology of the host, such as food intake and sleep/wake cycles. In recent years, an increasing amount of genetic and epidemiological data has shown that the light/dark cycle is the main cue that regulates circadian rhythms. Other factors, including sleep/wake cycles and food intake, have necessary effects on the composition and rhythms of the gut microbiota. Interestingly, the gut microbiota can affect the circadian rhythm of hosts in turn through contact-dependent and contact-independent mechanisms. Furthermore, the gut microbiota has been shown to regulate the sleep/wake cycles through gut-brain-microbiota interaction. In addition to diabetes, the gut microbiota can also intervene in the progression of neuro- degenerative diseases through the gut-brain-microbiota interaction, and also in other diseases such as hypertension and rheumatoid arthritis, where it is thought to have a spare therapeutic potential. Even though fecal microbiota transplantation has good potential for treating many diseases, the risk of spreading intestinal pathogens should not be ignored.

Stroke is a significant public health concern for elderly individuals. However, the majority of pre-clinical studies utilize young and healthy rodents, which may result in failure of candidate therapies in clinical trials. In this brief review/perspective, the complex link between circadian rhythms, aging, innate immunity, and the gut microbiome to ischemic injury onset, progression, and recovery is discussed. Short-chain fatty acids and nicotinamide adenine dinucleotide+ (NAD+ ) production by the gut microbiome are highlighted as key mechanisms with profound rhythmic behavior, and it is suggested to boost them as prophylactic/therapeutic approaches. Integrating aging, its associated comorbidities, and circadian regulation of physiological processes into stroke research may increase the translational value of pre-clinical studies and help to schedule the optimal time window for existing practices to improve stroke outcome and recovery.

The mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.

Fecal transplants from human infants with highly abundant Bifidobacterium , an important inhabitant of the intestinal tract of breastfed newborns, may promote brain connectivity in mice.

Recent explorations into the gut microbiome of humans and animals reveal implications in chronic physical and mental health disorders. Relatively little is known regarding the relationship of gut microbiome and depression. In the current review, we reviewed existing scientific data related to the gut microbiome and healthy patients versus patients with depression. Additionally, scientific literature containing the utility of microbiome interventions to improve depression symptoms was reviewed.

A PubMed and Clinical Key literature search combined the key terms 'gut,' 'microbiome,' 'bacteria,' and 'depression' to identify studies investigating these relationships.

76 relevant articles were identified. Human and animal studies reviewed examined marked alterations in the dominant bacterial phyla in the gut of individuals with depression, the connection between leaky gut and neuroinflammation in depression, brain regulatory centers impacted by changes in the gut microbiome, and the benefits of the addition of a probiotic/prebiotic for gut and mental health.

The current review confirmed the suspected direct communication between the gut microbiome, brain functioning, and depression. Additionally, studies suggest antibiotics disrupt the gut microbiome. There are important implications for psychiatrists in providing opportunities for intervention and enhancement of current treatments for individuals with depression.

This study assessed the associations of binge eating, compensatory behaviors, and dietary restraint with the composition and diversity of the intestinal microbiota among participants with binge-eating disorder or bulimia nervosa.

We analyzed data from 265 participants aged 18 to 45 years with current binge-eating disorder or bulimia nervosa enrolled in the Binge Eating Genetics Initiative study. We evaluated the associations of binge-eating frequency; presence/absence and frequency of vomiting, laxative use, and compulsive exercise; and dietary restraint with abundances of gut microbial genera, species, and diversity (Shannon diversity, Faith phylogenetic diversity, and Peilou's evenness) from 16S rRNA gene sequencing. General linear regression models adjusted for potential confounders, including age and current body mass index, were used to test associations; p values were corrected for the false discovery rate.

The normalized abundance of four genus- and species-level gut microbes and three diversity indices were lower among Binge Eating Genetics Initiative participants who reported any laxative use compared with those who reported no laxative use. Vomiting frequency was positively associated with the normalized abundance of the genus Escherichia-Shigella , a potential pathobiont, although the association was attenuated to nonsignificance after adjustment for age, body mass index, and binge-eating episodes.

Laxative use was highly and uniformly predictive of a reduced gut microbial diversity including potential commensals and pathobionts, and should be assessed and accounted for in all future studies of eating disorders and the gut microbiota. Future studies should collect data on specific medications-particularly laxatives-and dietary intake to obtain unbiased estimates of the effect of eating disorders on the gut microbiota and identify potential downstream clinical implications.Trial Registration:ClinicalTrials.gov identifier: NCT04162574 .

Cancers of the biliary tract are more common in Asia than in Europe, but are highly lethal due to delayed diagnosis and aggressive tumor biology. Since the biliary tract is in direct contact with the gut via the enterohepatic circulation, this suggests a potential role of gut microbiota, but to date, the role of gut microbiota in biliary tract cancers has not been elucidated. This scoping review compiles recent data on the associations between the gut microbiota and diagnosis, progression and prognosis of biliary tract cancer patients. Systematic review of the literature yielded 154 results, of which 12 studies and one systematic review were eligible for evaluation. The analyses of microbiota diversity indices were inconsistent across the included studies. In-depth analyses revealed differences between gut microbiota of biliary tract cancer patients and healthy controls, but without a clear tendency towards particular species in the studies. Additionally, most of the studies showed methodological flaws, for example non-controlling of factors that affect gut microbiota. At the current stage, there is a lack of evidence to support a general utility of gut microbiota diagnostics in biliary tract cancers. Therefore, no recommendation can be made at this time to include gut microbiota analyses in the management of biliary tract cancer patients.

Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.

Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and fecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animals and clinical studies assessing renal function, many of which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatization, baseline microbiota and its normalization, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best-practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardizing study designs, methods, and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.

The glyoxalase system includes glyoxalase I (GLXI), glyoxalase II (GLXII) and glyoxalase III (GLXIII), which are responsible for methylglyoxal (MG) detoxification and involved in abiotic stress responses such as drought, salinity and heavy metal.

In this study, a total of 620 GLX family genes were identified from 21 different plant species. The results of evolutionary analysis showed that GLX genes exist in all species from lower plants to higher plants, inferring that GLX genes might be important for plants, and GLXI and GLXII account for the majority. In addition, motif showed an expanding trend in the process of evolution. The analysis of cis-acting elements in 21 different plant species showed that the promoter region of the GLX genes were rich in phytohormones and biotic and abiotic stress-related elements, indicating that GLX genes can participate in a variety of life processes. In cotton, GLXs could be divided into two groups and most GLXIs distributed in group I, GLXIIs and GLXIIIs mainly belonged to group II, indicating that there are more similarities between GLXII and GLXIII in cotton evolution. The transcriptome data analysis and quantitative real-time PCR analysis (qRT-PCR) show that some members of GLX family would respond to high temperature treatment in G.hirsutum. The protein interaction network of GLXs in G.hirsutum implied that most members can participate in various life processes through protein interactions.

The results elucidated the evolutionary history of GLX family genes in plants and lay the foundation for their functions analysis in cotton.

The gut-brain axis refers to a bidirectional communication pathway linking the gastrointestinal system to the central nervous system. The hardware of this multifaceted pathway takes many forms, at once structural (neurons, microglia, intestinal epithelial cell barrier), chemical (neurotransmitters, enteroendocrine hormones, bacterial metabolites), and cellular (immune signaling, inflammatory pathways). The gut-brain axis is exquisitely influenced by our environment, diet, and behaviors. Here, we will describe recent progress in understanding the gut-brain axis in neurological disease, using Parkinson's disease as a guide. We will see that each component of the gut-brain axis is heavily mediated by intestinal microbiota and learn how gut-brain communication can go awry in microbial dysbiosis.

The aim of this review was to evaluate the feasibility of treating sleep disorders using novel gut microbiota intervention strategies. Multiple factors can cause sleep disorders, including an imbalance in the gut microbiota. Studies of the microbiome-gut-brain axis have revealed bidirectional communication between the central nervous system and gut microbes, providing a more comprehensive understanding of mood and behavioral regulatory patterns. Changes in the gut microbiota and its metabolites can stimulate the endocrine, nervous, and immune systems, which regulate the release of neurotransmitters and alter the activity of the central nervous system, ultimately leading to sleep disorders. Here, we review the main factors affecting sleep, discuss possible pathways and molecular mechanisms of the interaction between sleep and the gut microbiota, and compare common gut microbiota intervention strategies aimed at improving sleep physiology.

The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

In recent years, relevant studies have found changes in gut microbiota (GM) in patients with epilepsy. In addition, impaired sleep and circadian patterns are common symptoms of epilepsy. Moreover, the types of seizures have a circadian rhythm. Numerous reports have indicated that the GM and its metabolites have circadian rhythms. This review will describe changes in the GM in clinical and animal studies under epilepsy and circadian rhythm disorder, respectively. The aim is to determine the commonalities and specificities of alterations in GM and their impact on disease occurrence in the context of epilepsy and circadian disruption. Although clinical studies are influenced by many factors, the results suggest that there are some commonalities in the changes of GM. Finally, we discuss the links among epilepsy, gut microbiome, and circadian rhythms, as well as future research that needs to be conducted.

The timing of food intake is a key cue for circadian rhythms in humans and animals. In response to food intake, gut hormones called incretin are produced by intestinal enteroendocrine cells in a circadian rhythm that stimulates insulin secretion and regulates body weight and energy expenditure. Pregnancy is associated with the expansion of β cells, the risk of gestational diabetes mellitus, and excessive weight gain. The timing of food intake is a good way to address metabolic complications during pregnancy. The current review focuses on the circadian rhythms and biological actions of enteroendocrine hormones and their associations with pregnancy status, specifically topics like food intake and gut circadian rhythms, the circadian secretion of enteroendocrine peptides, and the effects of these factors during pregnancy.