Background Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. Results In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus , which were positively correlated with gut barrier function, while suppressing Odoribacter , Rikenella , Oscillibacter and Parasutterella , which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. Conclusions Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.
5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.
Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans, human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.
Cholesterol gallstone (CGS) disease is prevalent worldwide. None of the medical options for prevention and treatment of CGS disease are recommended, and surgical management has a high rate of recurrence.
Human breast milk Streptococcus spp. are transferred to infant guts via breast feeding, but their effects on the gut microbiota and immunity remain unclear. In this study, we characterized gut microbiota and immune modulatory properties of human breast milk S. salivarius F286 and S. parasanguinis F278 that had been shown to be able to colonize gut. The two Streptococcus strains were orally administered to mouse pups individually at 1 × 107 cells/day from postnatal Days 1 to 21. At postnatal week 3 (the weaning period), S. salivarius F286 reduced the colonic microbiota α-diversity, increased 21 amplicon sequence variants (ASVs), including bacteria from Akkermansia, Intestinimonas, and Lachnospiraceae, and decreased 52 ASVs, including bacteria from Eubacterium, Bifidobacterium, Escherichia-Shigella, and Turicibacter; however, S. parasanguinis F278 didn't change the colonic microbiota. Both Streptococcus strains reduced the ileal mRNA expression of cytokine/transcription factor representatives of T helper (Th) cells, including IFN-γ (Th1), Gata3 (Th2), and TGF-β (Treg) in 2-week-old suckling mice, and promoted the ileal expression of Foxp3 and TGF-β, which are representatives of anti-inflammatory Treg cells, in 3-week-old weaning mice. The two Streptococcus strains exhibited anti-inflammatory potential when incubated in vitro with human peripheral blood mononuclear cells and TNF-α-treated gut epithelial HT29 cells. In C. elegans, both strains activated immune response genes, which was associated with their lifespan-prolonging effects. Our results suggest that S. salivarius F286 and S. parasanguinis F278 may exert regulatory (anti-inflammatory) roles in gut immunity and S. salivarius F286 can modulate gut microbiota, and highlight the probiotic potential of milk S. salivarius and S. parasanguinis strains.
OBJECTIVE:The association of the gut microbiome with bone turnover markers (BTMs) in postmenopausal women is poorly understood.METHODS:Fecal samples were collected from 97 Chinese postmenopausal women, and the serum CTX and P1NP were determined. Individuals with serum CTX lower or higher than the median value were divided into LCTX and P1NP groups; and individuals with serum P1NP lower or higher than the median value were grouped into LP1NP and HP1NP groups. Microbiota profiles were determined by high-throughput 16S rRNA gene sequencing.RESULTS:In postmenopausal women, only Faecalibacterium showed significant alteration in the HCTX group compared with the LCTX group (P=0.004, q=0.143). Linear discriminant analysis effect size (LEfSe) analysis revealed that Clostridiaceae (P=0.015, LDA=2.89), Faecalibacterium (P=0.017, LDA=4.60), Prevotella (P=0.040, LDA=3.61) and Clostridium (P=0.007, LDA=2.79) were abundant in the LCTX group, and Facklamia (P=0.044, LDA=3.10) was enriched in the HCTX group. Peptostreptococcaceae (P=0.048, LDA=2.83) and the SMB53 (P=0.028, LDA=2.05) genus were enriched in the LPINP group, and Veillonellaceae (P=0.025, LDA=4.43) and the S24_7 (P=0.023, LDA=3.08) family were enriched in the HPINP group. Six taxa correlated with BTMs in all subjects, including Clostridium (Clostridiaceae) that was negatively correlated with serum CTX amounts significantly (r=-0.34, P<0.001).CONCLUSION:This study identified taxa-specific differences in the intestinal microflora associated with BTMs, notably CTX. These findings may help in uncovering the roles of gut microbiota on bone metabolism.
在线虫-细菌模型中,常用控制起始线虫无菌的方法有两种:解体母虫获取虫卵或直接冲洗成虫.本研究采用野生型N2虫株,标准食物菌株E.coli OP50和一株试验菌株T.B,设立单平板线虫-双菌苔选择模型.发现采用严格无菌虫卵设立试验模型时,虫体在不同菌株之间不表现偏好性,纵向比较不同虫龄之间(L2或L3,L4,成虫)的选择行为也没有显著差异.此外,从虫卵到成年的发育过程中虫体的健康状态不一致.采用M9缓冲液冲洗的成虫来设立试验,能够保证虫体在做出选择行为前健康状态相同、虫龄一致,数据显示成虫在8~16h后对不同菌苔之间表现显著的偏好性,并且选择行为稳定.因此,在研究线虫对不同菌苔偏好性选择行为的模型中,应采取冲洗的成虫来设立试验.
Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium, Staphylococcus, Lactobacillus, and Escherichia/Shigella. Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium, Prevotella, Roseburia, Ruminococcus, and Bacteroides, was 0.01–1% in the milk inoculum and 0.003–0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003–0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.
The transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth-weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome.
BACKGROUND Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined. OBJECTIVE The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health. DESIGN The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers. RESULTS Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of >100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation. CONCLUSIONS These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353.
Emerging evidence suggests novel cardiometabolic roles for bacterially-synthesized vitamin K forms known as menaquinones (MK-n). Though gut bacteria synthesize MK-n, relationships between gut microbiota composition, MK-n biosynthesis, and cardiometabolic health have not been examined. To examine these relationships, MK-n and microbiota composition were measured in fecal samples collected from 77 Chinese adults (41 ± 7 y, BMI 32 ± 2 kg/m2) during a 23-wk diet intervention previously shown to alter gut microbiota composition and improve cardiometabolic health. Variability in fecal MK-n content was associated with gut microbiota composition, and longitudinal changes in the relative abundance of > 100 phylotypes were associated with altered fecal content of 蠅 1 individual MK-n. The strongest and most consistent relationships were between Prevotella spp. and MK-5, -11 -12, and -13, between Bacteroides spp. and MK-9 and -10, and between Eschericia/Shigella spp. and MK-8. Baseline fecal MK-9 content was inversely associated with BMI (r = -.30, P = 0.05) and HOMA-IR (r = -.37, P = 0.01). No other cross-sectional or longitudinal associations between fecal MK-n and cardiometabolic health biomarkers were observed. Findings suggest that variability in fecal MKn content is associated with the gut microbiota, and that diet-mediated changes in gut microbiota composition may alter gut MK-n content. The implications for human health merit further investigation. Funding: Dr. James Sadowski Memorial Internship, USDA contract #58-1950-7-707, National Nature Science Foundation of China.
This study was carried on about soil moisture and nutrients of meadow steppe, typical steppe and desert steppe ecosystems. The results showed that meadow steppes had the maximum soil moisture content, while the desert steppes had the minimum. This was because the three types of steppes had different soil types and physical characteristics, and these physical characteristics influenced soil moisture content to some extent. Compared with that in the meadow steppes and desert steppes, carbon and nitrogen content of soil of the typical steppes were the highest, and the differences in soil carbon and nitrogen among the three types of steppes were significant or obviously significant. They were due to the geographical environments, temperature and precipitation caused by a combination of factors.
In order to study the impact of stone mineral composition and micro-structure on its frictional properties, 3 pavement stones used commonly were selected and researched experimentally. In the research, the frictions were measured by the specially designed facility of the State Key Laboratory of Tsinghua University and the mineral characteristics were conducted by the flake inspection, respectively. In addition, the Polishing Stone Value, abrasion value, impact value and crushing value of the 3 stones was tested. The results denote that the broader the size distributing range of compositing minerals and the greater the hardness, the larger the frictional coefficient, which indicates the mineral characteristics of pavement stones are especially essential for frictional property.