Statin-induced gut dysbiosis and sleep disturbances: Mechanistic insights into microbiota–brain–circadian interactions and chronotherapeutic implications

Is CYP2C70 the key to new mouse models to understand bile acids in humans?

The Benevolent Bile: Bile Acids as Stimulants of Liver Regeneration

Hypoglycemic effects of different molecular weight konjac glucomannans via intestinal microbiota and SCFAs mediated mechanism

BackgroundMenstrual disturbances harm women’s health, and general well-being. As growing evidence highlights the relationship between sleep and menstrual disturbances, it is imperative to comprehensively examine the association between sleep and menstrual disturbance considering the multiple dimensions of sleep. This systematic review aims to identify the association between sleep and menstrual disturbances by evaluating using Buysse’s sleep health framework.MethodsA comprehensive search of the literature was conducted in PubMed, EMBASE, psychINFO, and CINAHL to identify publications describing any types of menstrual disturbances, and their associations with sleep published between January 1, 1988 to June 2, 2022. Quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. The findings were iteratively evaluated menstrual disturbances and their association with sleep using Buysse’s sleep health framework. This framework understands sleep as multidimensional concept and provides a holistic framing of sleep including Satisfaction, Alertness during waking hours, Timing of sleep, Efficiency, and Sleep duration. Menstrual disturbances were grouped into three categories: premenstrual syndrome, dysmenorrhea, and abnormal menstrual cycle/heavy bleeding during periods.ResultsThirty-five studies were reviewed to examine the association between sleep and menstrual disturbances. Premenstrual syndrome and dysmenorrhea were associated with sleep disturbances in sleep health domains of Satisfaction (e.g., poor sleep quality), Alertness during waking hours (e.g., daytime sleepiness), Efficiency (e.g., difficulty initiating/maintaining sleep), and Duration (e.g., short sleep duration). Abnormal menstrual cycle and heavy bleeding during the period were related to Satisfaction, Efficiency, and Duration. There were no studies which investigated the timing of sleep.Conclusions/ImplicationsSleep disturbances within most dimensions of the sleep health framework negatively impact on menstrual disturbances. Future research should longitudinally examine the effects of sleep disturbances in all dimensions of sleep health with the additional objective sleep measure on menstrual disturbances. This review gives insight in that it can be recommended to provide interventions for improving sleep disturbances in women with menstrual disturbance.

IntroductionRecent studies demonstrated that the gut microbiome of Parkinson's Disease (PD) patients differs from that of age-matched healthy controls. Notably less butyrate-producing bacteria and low mucosal and fecal short chain fatty acid (SCFA) concentrations were found in PD patients. SCFA play a role in the interplay of health and disease: SCFA butyrate improves colon motility, protects the colonic epithelium and reduces inflammation. Administration of butyrate in animal models of PD improved motor impairment and dopamine deficiency and reduced early mortality. We hypothesize that certain orally supplemented dietary fibers can stimulate butyrate production in the colon of Parkinson's patients, and consequently can improve the motor impairment and their quality of life. This hypothesis still requires a step-wise approach. Our objective is to investigate the effect of different types of dietary fiber on the gut microbiota and SCFA production in PD patients and healthy elderly.Material and methodsPD patients and healthy controls (HC) were selected based on age (55–70 years old) and BMI (18.5 -25 kg/m2). For PD patients the Hoehn and Yahr score (I – III) was added to this selection. The effect of inulin varying in degree of polymerization (DP) (average DP ~10 vs. average DP ~23) on the SCFA production was evaluated by ex vivo fermentation experiments with fecal samples of PD patients and HC. Inulin (1% w/v) was incubated in small-scale batch fermentations for 24 h at 37°C in anaerobic conditions. SCFA production was analyzed by solid phase micro-extraction capillary gas chromatography-mass spectrometry detection (SPME-cGS-MS). The clostridia clusters IV and XIVa were quantified through 16s qPCR.Results and discussionShort chain (Sc) and long chain(Lc) inulin fermentation resulted in a mean total SCFA increase of respectively 490.3 ± 128.2μmol/ml and 384.3 ± 85.9μmol/ml in HC (n = 7) and 453.9 ± 99.2μmol/ml and 402.9μmol/ml ± 84.1μmol/ml in PD patients (n = 3). Sc inulin fermentation increased butyrate production with 200.0μg/ml ± 46.2μmol/ml in HC and 119.8 ± 94.4μg/ml in PD patients (p = 0.09). Lc inulin fermentation increased butyrate production with 174.9μmol/ml ± 82.2μmol/ml and 113.3μmol/ml ± 21.2μmol/ml in HC and PD patients, respectively (p = 0.25). Large variation between samples was observed in PD patients.ConclusionAlthough sample size is relatively small and data is still collected, we can conclude that both Sc and Lc inulin increase total SCFA and butyrate production in HC and PD patients. This ex vivo study shows that stimulation of the butyrate production is still possible in PD patients and could be beneficial.

Bile acid metabolism and signaling: Emerging pharmacological targets of dietary polyphenols

The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis. A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species. Notably, increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation. Key microbial metabolites such as short-chain fatty acids (SCFAs) influence lipid metabolism through multiple pathways, including the activation of GPR41/43 receptors, modulation of the bile acid–FXR/TGR5 axis, and regulation of hepatic lipogenesis. Additionally, the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling. This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii—in fat metabolism. We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production, bile acid signaling, and AMPK/PPAR-related pathways. These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance, offering novel opportunities for applications in health management, nutritional interventions, and microbial therapeutics.Graphical

BackgroundGut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.ResultsEight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.ConclusionsOur results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.

Radix Angelica dahuricae extract ameliorates oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats by modulating the gut microbiota and bile acid signalling

Fibroblast Growth Factor Signaling Controls Liver Size in Mice With Humanized Livers

Short chain and medium chain fatty acids production using food waste under non-augmented and bio-augmented conditions

Objectives:We hypothesized that short chain fatty acid (SCFA) production by oral pathogens is suppressed by exposure to cigarette smoke extract (CSE).Background:Tobacco smoking is a major risk factor for plaque-induced periodontal diseases. Despite increased disease susceptibility, overt oral inflammation is suppressed in smokers, presenting a diagnostic conundrum. Bacterial-derived SCFAs can penetrate into oral tissues where they influence multiple components of immune and healing responses. Indeed, the SCFA burden has been correlated with the inflammatory condition of the gingiva. However, the influence of cigarette consumption on SCFA production is unknown.Methods:GC/MS was employed to monitor the production of several SCFAs (propionic acid, isobutyric acid, butyric acid, isovaleric acid) by representative anaerobic oral pathogens (Filifactor alocis 35896, Fusobacterium nucleatum 25586, Porphyromonas gingivalis 33277) that were exposed, or not, to a physiologically relevant dose of CSE (2000 ng /ml nicotine equivalents) generated from 3R4F reference cigarettes.Results:The growth of all three bacterial species was unaffected by CSE. The capacity to produce SCFAs by these bacteria was highly varied. F. alocis produced the highest concentration of a specific SCFA (butyrate); P. gingivalis provided the most robust overall SCFA signal, while F. alocis and F. nucleatum did not release detectable levels of isobutyrate or isovalerate. As P. gingivalis 33277 was the broadest SCFA producer, three low passage clinical isolates (10208C, 5607 and 10512) were also examined. Compared to unconditioned microbes, reduced SCFA release was apparent in CSE-exposed low passage clinical isolates of P. gingivalis which reached significance for one of the three isolates (propionic, isobutyric, butyric and isovaleric acids, all p < 0.05).Conclusions:There is high disparity in the SCFA profiles of variant chronic periodontitis-associated bacteria, while CSE exposure reduces SCFA production by a specific clinical strain of P. gingivalis. If the latter phenomenon occurs in vivo, a reduced SCFA burden may help explain the reduced vascular response to dental plaque in tobacco smokers.

Introduction Black sexual minority men (SMM) suffer disproportionately from health inequities, including high rates of HIV, as well as poor mental and physical health. In addition to intersectional stigma and discrimination, sleep health, an understudied factor, may contribute to these health inequities. We examined the associations between coping with discrimination, sleep disturbances, and mental and behavioral health outcomes among Black SMM. Methods We recruited 191 Black SMM participants both in person at community-based events and organizations and online. Sleep disturbance, depression, anxiety, alcohol use, and quality of life were measured using PROMIS-Sleep Disturbance, Physical Health Questionnaire, Generalized Anxiety Disorder, Alcohol Use Disorders Identification Test, and PROMIS global health items. Experience of and coping with discrimination were measured using validated questionnaires. Regression and mediation analysis were conducted, controlling for age. Results One-quarter of the sample reported elevated levels of sleep disturbance. Experiences of racial discrimination were marginally associated with greater sleep disturbances (b = 0.59, p = 0.07). Effective coping (e.g., getting emotional support, thinking about steps to take) (b = -2.62, p = 0.03) and higher coping self-efficacy (b = -2.00, p &amp;lt; 0.001) were associated with fewer sleep disturbances. Less effective coping (e.g., self-blame, denial) was associated with more sleep disturbances (b = 4.70, p = 0.009). Greater sleep disturbance was associated with higher ratings of depression (b = 0.04, p &amp;lt; 0.001), anxiety (b = 0.03, p &amp;lt; 0.001) and lower ratings of quality of life (b = -0.04, p &amp;lt; 0.001), and marginally with greater alcohol use disturbances (b = 0.12, p = 0.06). Indirect paths via sleep disturbance were significant for the effects of effective coping or ineffective coping on depression, anxiety, alcohol use (for ineffective coping only), and quality of life. Conclusion Effective coping strategies appeared to mitigate sleep disturbances and other health challenges, underscoring the need for culturally congruent interventions that address both sleep and mental health to improve overall wellbeing in this population. Additionally, it is imperative to actively address intersectional stigma and discrimination. Mediation analysis was based on cross-sectional data and should be interpreted with caution. Support (if any) This work is supported by NIMHD R01MD014722 (LMB)

Rural sleep health and sleep health disparities among children and adults in the United States.

Improved bioproduction of short-chain fatty acids from waste activated sludge by perennial ryegrass addition