Background COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. Methods To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. Results Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. Conclusions Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

Previous meta-analysis studies have indicated inverse associations between some carotenoids and risks of metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. However, the results for associations between carotenoids and type 2 diabetes (T2D) remain inconsistent and no systematic assessment has been done on this topic. We conducted a systematic review and meta-analysis to examine the associations of dietary intakes and circulating concentrations of carotenoids with risk of T2D. We searched PubMed and Ovid Embase from database inception to July 2020. Prospective observational studies of carotenoids and T2D risk were included. Random-effects models were used to summarize the RRs and 95% CIs. Thirteen publications were included. Dietary intake of β-carotene was inversely associated with the risk of T2D, and the pooled RR comparing the highest with the lowest categories was 0.78 (95% CI: 0.70, 0.87; I2 = 13.7%; n = 6); inverse associations were also found for total carotenoids (n = 2), α-carotene (n = 4), and lutein/zeaxanthin (n = 4), with pooled RRs ranging from 0.80 to 0.91, whereas no significant associations were observed for β-cryptoxanthin and lycopene. Circulating concentration of β-carotene was associated with a lower risk of T2D, and the pooled RR comparing extreme categories was 0.60 (95% CI: 0.46, 0.78; I2 = 56.2%; n = 7); inverse associations were also found for total carotenoids (n = 3), lycopene (n = 4), and lutein (n = 2), with pooled RRs ranging from 0.63 to 0.85, whereas no significant association was found for circulating concentrations of α-carotene and zeaxanthin when comparing extreme categories. Dose-response analysis indicated that nonlinear relations were observed for circulating concentrations of α-carotene, β-carotene, lutein, and total carotenoids (all P-nonlinearity < 0.05), but not for other carotenoids or dietary exposures. In conclusion, higher dietary intakes and circulating concentrations of total carotenoids, especially β-carotene, were associated with a lower risk of T2D. More studies are needed to confirm the causality and explore the role of foods rich in carotenoids in prevention of T2D. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42020196616.

STUDY QUESTION Is physical activity or sedentary time associated with semen quality parameters? SUMMARY ANSWER Among healthy men screened as potential sperm donors, higher self-reported physical activity was associated with increased progressive and total sperm motility. WHAT IS KNOWN ALREADY Despite the claimed beneficial effect of moderate physical activity on semen quality, results from epidemiological studies have been inconclusive. Previous studies were mostly conducted among endurance athletes or male partners of couples who sought infertility treatment. STUDY DESIGN, SIZE, DURATION Healthy men screened as potential sperm donors were recruited at the Hubei Province Human Sperm Bank of China. Between April 2017 and July 2018; 746 men completed the long-form International Physical Activity Questionnaire (IPAQ) and provided repeated semen samples (n = 5252) during an approximately 6-month period. PARTICIPANTS/MATERIALS, SETTING, METHODS Total metabolic equivalents (METs), moderate-to-vigorous METs and sedentary time were abstracted from the IPAQ. Sperm concentration, total sperm count, progressive motility and total motility in repeated specimens were determined by trained clinical technicians. Mixed-effect models were applied to investigate the relationships between physical activity and sedentary time and repeated measures of semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE After adjusting for multiple confounders, total METs and moderate-to-vigorous METs were both positively associated with progressive and total sperm motility. Compared with men in the lowest quartiles, those in the highest quartiles of total and moderate-to-vigorous METs had increased progressive motility of 16.1% (95% CI: 6.4, 26.8%) and 17.3% (95% CI: 7.5, 27.9%), respectively, and had increased total motility of 15.2% (95% CI: 6.2, 24.9%) and 16.4% (95% CI: 7.4, 26.1%), respectively. Sedentary time was not associated with semen quality parameters. LIMITATIONS, REASONS FOR CAUTION The IPAQ was reported only once from study participants; measurement errors were inevitable and may have biased our results. Furthermore, although we have adjusted for various potential confounders, the possibility of unmeasured confounding cannot be fully ruled out. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that maintaining regular exercise may improve semen quality parameters among healthy, non-infertile men. Specifically, we found that higher self-reported total and moderate-to-vigorous METs were associated with improved sperm motility, which reinforces the existing evidence that physical activity may improve male reproductive health. STUDY FUNDING/COMPETING INTEREST(S) Y.-X.W was supported by the Initiative Postdocs Supporting Program (No. BX201700087). A.P. was supported by the National Key Research and Development Program of China (2017YFC0907504). C.-L.X. was supported by the National Key Research and Development Program of China (2016YFC1000206). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.