Chronic kidney disease (CKD) is often accompanied with colon mucosal barrier damage and gut microbiota disturbance, which strongly associate with up-regulated inflammation and kidney tubulointerstitial fibrosis. However, few interventions could protect the damaged barrier effectively. Rheum palmatum L or rhubarb is a common herbal medicine which is widely used to protect the colon mucosal barrier. In previous studies, we found that rhubarb intervention may reduce renal inflammation and tubulointerstitial fibrosis, via gut microbiota modification. However, whether intestinal barrier function could be improved by rhubarb intervention and the relationship with intestinal flora are still unknown. Therefore, we investigated the effects of rhubarb enema on intestinal barrier, and further analyzed the relationship with gut microbiota in 5/6 nephrectomy rats. Results indicated that rhubarb enema improved the intestinal barrier, regulated gut microbiota dysbiosis, suppressed systemic inflammation, and alleviated renal fibrosis. More specifically, rhubarb enema treatment inhibited the overgrowth of conditional pathogenic gut bacteria, including Akkermansia, Methanosphaera, and Clostridiaceae in CKD. The modification of gut microbiota with rhubarb intervention displayed significant correlation to intestinal barrier markers, TLR4-MyD88-NF-kB inflammatory response, and systemic inflammation. These results revealed that rhubarb enema could restore intestinal barrier by modifying several functional enteric bacteria, which may further explain the renal protection mechanism of the rhubarb enema.

Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut microbiota has been proposed to mediate IBS; however, contradictory results exist, and IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.

In Guangzhou, China, whether the trend of a decreasing pubertal age has continued in recent years remained unknown, and the association between obesity and early puberty was still controversial. Herein, we conducted a serial cross-sectional study using data from physical fitness surveillance (2005–2012), to determine the recent trends in age at spermarche and menarche among students in Guangzhou, and to investigate whether elevated BMI modified timing of spermarche and menarche. This study included 1,278,258 urban students. In boys, no significant differences were observed in median ages of spermarche (MAS) from 2005 to 2012, with overlapping 95% CIs. Similar results were observed for median ages of menarche (MAM) in girls. The Cox-Stuart trend test showed neither upward nor downward shift in MAS and MAM over time (P = 0.625; 1.000). Each year, both MAS and MAM decreased with increasing BMI. Furthermore, a higher BMI was associated with early age at spermarche and menarche, with ORs of 1.052 (95% CI = 1.045–1.059) and 1.233 (95% CI = 1.220–1.247) in 2012 for boys and girls, respectively. In conclusion, the pubertal timing has been stable in urban students from 2005 to 2012. Furthermore, obesity was associated with early timing of spermarche and menarche.

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography–mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.