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Journal of Pharmaceutical Analysis Feb 2024The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3...
The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as and , and clearance of pathogenic . Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.
PubMed: 38464791
DOI: 10.1016/j.jpha.2023.09.010 -
Frontiers in Microbiology 2024Hildenborough is a gram-negative anaerobic bacterium belonging to the sulfate-reducing bacteria that exhibits highly versatile metabolism. By switching from one energy...
INTRODUCTION
Hildenborough is a gram-negative anaerobic bacterium belonging to the sulfate-reducing bacteria that exhibits highly versatile metabolism. By switching from one energy mode to another depending on nutrients availability in the environments" it plays a central role in shaping ecosystems. Despite intensive efforts to study energy metabolism at the genomic, biochemical and ecological level, bioenergetics in this microorganism remain far from being fully understood. Alternatively, metabolic modeling is a powerful tool to understand bioenergetics. However, all the current models for appeared to be not easily adaptable to various environmental conditions.
METHODS
To lift off these limitations, here we constructed a novel transparent and robust metabolic model to explain bioenergetics by combining whole-cell proteomic analysis with modeling approaches (Flux Balance Analysis).
RESULTS
The iDvu71 model showed over 0.95 correlation with experimental data. Further simulations allowed a detailed description of metabolism in various conditions of growth. Altogether, the simulations run in this study highlighted the sulfate-to-lactate consumption ratio as a pivotal factor in energy metabolism.
DISCUSSION
In particular, the impact on the hydrogen/formate balance and biomass synthesis is discussed. Overall, this study provides a novel insight into metabolic flexibility.
PubMed: 38463485
DOI: 10.3389/fmicb.2024.1336360 -
Frontiers in Microbiology 2024Traditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body 's immunity and changes in intestinal...
BACKGROUND
Traditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body 's immunity and changes in intestinal flora. This study was conducted to investigate the effects of dietary Hong-bailanshen (HBLS) supplementation in horses on serum biochemical profile, antioxidant enzymes and gut microbiota.
METHODS
In this study, five horses were selected. On day 0, 14, 28, blood samples and feces were collected on days 0, 14, and 28 to analyse gut microbiota, serum biochemical and redox indexes.
RESULTS
The results showed that the addition of HBLS to horse diets significantly decreased the level of alanine aminotransferase, alkaline phosphatase, creatine kinase and malondialdehyde ( < 0.05, < 0.01) and significantly increased the activity of total antioxidant capacity, superoxide dismutase and catalase ( < 0.05, < 0.01). Compared with day 14, the levels of alanine aminotransferase, alkaline phosphatase and creatine kinase were significantly decreased; however, the level of catalase was significantly increased in the horses continuously fed with HBLS for 28 days ( < 0.05, < 0.01). Alpha diversity analysis was performed that chao1 ( < 0.05), observed_specicies, faith'pd and goods_coverage upregulated in the horses fed HBLS. A total of 24 differential genera were detected adding HBLS to diet increased the abundance of and , while reduced and ( < 0.05, < 0.01).
CONCLUSION
Adding HBLS to the diet could be a potentially effective strategy to improve horses' health.
PubMed: 38444806
DOI: 10.3389/fmicb.2024.1327210 -
Translational Animal Science 2024is a Chinese medicine with a long history in which stems and leaves are the wastes of processing and have not been effectively utilized. The effects of diets...
is a Chinese medicine with a long history in which stems and leaves are the wastes of processing and have not been effectively utilized. The effects of diets containing stems and leaves on the cecal short-chain fatty acid (SCFA) concentration and microbiome of independent pigs were studied. Diets containing stems and leaves did not affect the concentration of SCFA in the cecal contents of Duzang pigs but affected the microbial composition and diversity. Firmicutes, Proteobacteria, and Bacteroidetes dominate in the cecal of Duzang pigs. Feeding Duzang pigs with a 10% stems and leaves diet increases the abundance of , , and in the cecal. We found 14 genera positively associated with acetate, and they were , , and showed negative correlations. , , and were positively associated with propionate. , , and were positively associated with butyrate. In conclusion, stems and leaves could affect the cecal microbial community and functional composition of Duzang pigs. stems and leaves reduce the enrichment of lipopolysaccharide biosynthetic pathway of the cecal microbiome, which may have a positive effect on intestinal health. The higher abundance of GH25 family in Duzang pig's cecal microbiome of fed stems and leaves diet. This increase may be the reason for the microbial diversity decrease.
PubMed: 38425544
DOI: 10.1093/tas/txad142 -
Heliyon Feb 2024Curcumin is widely used as a traditional drug in Asia. Interestingly, curcumin and its metabolites have been demonstrated to influence the microbiota. However, the...
Curcumin is widely used as a traditional drug in Asia. Interestingly, curcumin and its metabolites have been demonstrated to influence the microbiota. However, the effect of curcumin on the gut microbiota in patients with myasthenia gravis (MG) remains unclear. This study aimed to investigate the effects of curcumin on the gut microbiota community, short-chain fatty acids (SCFAs) levels, intestinal permeability, and Th17/Treg balance in a Torpedo acetylcholine receptor (T-AChR)-induced MG mouse model. The results showed that curcumin significantly alleviated the clinical symptoms of MG mice induced by T-AChR. Curcumin modified the gut microbiota composition, increased microbial diversity, and, in particular, reduced endotoxin-producing Proteobacteria and Desulfovibrio levels in T-AChR-induced gut dysbiosis. Moreover, we found that curcumin significantly increased fecal butyrate levels in mice with T-AChR-induced gut dysbiosis. Butyrate levels increased in conjunction with the increase in butyrate-producing species such as Oscillospira, Akkermansia, and Allobaculum in the curcumin-treated group. In addition, curcumin repressed the increased levels of lipopolysaccharide (LPS), zonulin, and FD4 in plasma. It enhanced Occludin expression in the colons of MG mice induced with T-AChR, indicating dramatically alleviated gut permeability. Furthermore, curcumin treatment corrected T-AChR-induced imbalances in Th17/Treg cells. In summary, curcumin may protect mice against myasthenia gravis by modulating both the gut microbiota and SCFAs, improving gut permeability, and regulating the Th17/Treg balance. This study provides novel insights into curcumin's clinical value in MG therapy.
PubMed: 38420408
DOI: 10.1016/j.heliyon.2024.e26030 -
Microbiology Spectrum Apr 2024Neuroblastoma (NB) is a type of neuroectodermal tumor that originates from primitive sympathetic ganglion cells. Although many risk factors contributing to the... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Neuroblastoma (NB) is a type of neuroectodermal tumor that originates from primitive sympathetic ganglion cells. Although many risk factors contributing to the occurrence of NB have been reported in recent years, the role of the gut microbiota in its development remains unclear. A bidirectional Mendelian randomization (MR) analysis was conducted to elucidate the causal relationship between the gut microbiota and NB. In the MR analysis, we employed the inverse-variance weighted (IVW) method as the primary criterion for assessing causality, while also utilizing three additional approaches, including MR-Egger, weighted median model, and weighted mode, for comprehensive evaluation. For gut microbiota that were causally associated with NB, a reverse MR was also used to assess the stability of this causal relationship. Finally, we also used external cohorts for validation and performed a meta-analysis of the results. The IVW results indicated a causal relationship between six gut microbiota and NB. Among the six gut microbiota, genus [IVW odds ratio (OR): 2.66, 95% confidence interval (CI): 1.09-6.51, value: 0.03] exhibited a detrimental effect against NB. On the other hand, the class (IVW OR: 0.24, 95% CI: 0.07-0.77, value: 0.02), the family (IVW OR: 0.40, 95% CI: 0.17-0.96, value: 0.04), the genus (IVW OR: 0.50, 95% CI: 0.25-0.97, value: 0.04), the genus (IVW OR: 0.39, 95% CI: 0.16-0.92, value: 0.03), and the genus (IVW OR: 0.55, 95% CI: 0.31-0.97, value: 0.04) displayed a protective effect on NB. A reverse MR analysis did not reveal a causality between NB and the six gut microbiota. Meta-analysis showed that genus (meta OR: 0.41, 95% CI: 0.22-0.75, < 0.01) and genus (meta OR: 2.20, 95% CI: 1.01-4.79, < 0.05) were still significant.
IMPORTANCE
Bidirectional Mendelian randomization was used to explore the causality between gut microbiota and neuroblastoma (NB). The results showed that there is a causal relationship between the six gut microbiota and NB, of which two gut microbiota were further confirmed in the meta-analysis. This may provide a new perspective on the prevention and treatment of NB.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Neuroblastoma; Risk Factors; Actinobacteria; Bifidobacterium; Clostridiales; Genome-Wide Association Study
PubMed: 38411074
DOI: 10.1128/spectrum.03656-23 -
Microbiology Spectrum Apr 2024Insulin resistance is the primary pathophysiological basis for metabolic syndrome and type 2 diabetes. Gut microbiota and microbiota-derived metabolites are pivotal in...
UNLABELLED
Insulin resistance is the primary pathophysiological basis for metabolic syndrome and type 2 diabetes. Gut microbiota and microbiota-derived metabolites are pivotal in insulin resistance. However, identifying the specific microbes and key metabolites with causal roles is a challenging task, and the underlying mechanisms require further exploration. Here, we successfully constructed a model of insulin resistance in mice induced by a high-fat diet (HFD) and screened potential biomarkers associated with insulin resistance by integrating metagenomics and untargeted metabolomics. Our findings showed a significant increase in the abundance of 30 species of in HFD mice compared to normal diet (ND) mice, while the abundance of and was significantly lower in HFD mice than in ND mice. Non-targeted metabolomics analysis identified 21 insulin resistance-associated metabolites, originating from the microbiota or co-metabolized by both the microbiota and the host. These metabolites were primarily enriched in aromatic amino acid metabolism (tryptophan metabolism, tyrosine metabolism, and phenylalanine metabolism) and arginine biosynthesis. Further analysis revealed a significant association between the three distinct genera and 21 differentiated metabolites in the HFD and ND mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of representative genomes from 12 species of the three distinct genera further revealed the functional potential in aromatic amino acid metabolism and arginine biosynthesis. This study lays the groundwork for future investigations into the mechanisms through which the gut microbiota and its metabolites impact insulin resistance.
IMPORTANCE
In this study, we aim to identify the microbes and metabolites linked to insulin resistance, some of which have not been previously reported in insulin resistance-related studies. This adds a complementary dimension to existing research. Furthermore, we establish a correlation between alterations in the gut microbiota and metabolite levels. These findings serve as a foundation for identifying the causal bacterial species and metabolites. They also offer insights that guide further exploration into the mechanisms through which these factors influence host insulin resistance.
Topics: Animals; Mice; Insulin Resistance; Diet, High-Fat; Diabetes Mellitus, Type 2; Metabolomics; Biomarkers; Amino Acids, Aromatic; Arginine
PubMed: 38411058
DOI: 10.1128/spectrum.04094-23 -
Nature Water May 2023Chlorinated polyfluorocarboxylic acids (Cl-PFCAs) derived from the widely used chlorotrifluoroethylene (CTFE) polymers and oligomers may enter and influence the aquatic...
Chlorinated polyfluorocarboxylic acids (Cl-PFCAs) derived from the widely used chlorotrifluoroethylene (CTFE) polymers and oligomers may enter and influence the aquatic environment. Here, we report significant defluorination of Cl-PFCAs by an anaerobic microbial community via novel pathways triggered by anaerobic microbial dechlorination. Cl-PFCAs first underwent microbial reductive, hydrolytic, and eliminative dechlorination, and it was the hydrolytic dechlorination that led to significant spontaneous defluorination. Hydrolytic dechlorination was favored with increased Cl-substitutions. An isolated, highly enriched anaerobic defluorinating culture was dominated by two genomes closest to and , both of which exhibited active defluorination of CTFE tetramer acid. It implies the critical role played by anaerobic non-respiratory hydrolytic dechlorination in the fate of chlorinated polyfluoro-chemicals in natural and engineered water environments. The greatly enhanced biodegradability by Cl-substitutions also sheds light on the design of cost-effective treatment biotechnologies, as well as alternative PFAS that are readily biodegradable and less toxic.
PubMed: 38405335
DOI: 10.1038/s44221-023-00077-6 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism in...
Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism in relieving the clinical symptoms is unclear. Several lines of evidence point to a strong link between constipation and gut microbiota. Short-chain fatty acids (SCFAs) and microbial metabolites have been shown to affect 5-HT synthesis by activating the GPR43 receptor localized on intestinal enterochromaffin cells, since 5-HT receptors are known to influence colonic peristalsis. The objective of this study was to evaluate the efficacy of XCQ in alleviating clinical symptoms in a mouse model of STC induced by loperamide. The application of loperamide leads to a decrease in intestinal transport and fecal water, which is used to establish the animal model of STC. In addition, the relationship between constipation and gut microbiota was determined. The herbal materials, composed of Rhei Radix et Rhizoma (Rhizomes of L., Polygonaceae) 55.2 g, Magnoliae Officinalis Cortex (Barks of Rehd. et Wils, Magnoliaceae) 27.6 g, and Aurantii Fructus Immaturus (Fruitlet of L., Rutaceae) 36.0 g, were extracted with water to prepare the XCQ decoction. The constipated mice were induced with loperamide (10 mg/kg/day), and then treated with an oral dose of XCQ herbal extract (2.0, 4.0, and 8.0 g/kg/day) two times a day. Mosapride was administered as a positive drug. In loperamide-induced STC mice, the therapeutic parameters of XCQ-treated mice were determined, i.e., (i) symptoms of constipation, composition of gut microbiota, and amount of short-chain fatty acids in feces; (ii) plasma level of 5-HT; and (iii) expressions of the GPR43 and 5-HT4 receptor in colon. XCQ ameliorated the constipation symptoms of loperamide-induced STC mice. In gut microbiota, the treatment of XCQ in STC mice increased the relative abundances of , , , , and in feces and decreased the relative abundances of , , and . The levels of SCFAs in stools from the STC group were significantly lower than those the control group, and were greatly elevated via treatment with XCQ. Compared with the STC group, XCQ increased the plasma level of 5-HT and the colonic expressions of the GPR43 and 5-HT4 receptor, significantly. The underlying mechanism of XCQ in anti-constipation could be related to the modulation of gut microbiota, the increase in SCFAs, the increase in plasma 5-HT, and the colonic expressions of the GPR43 and 5-HT4 receptor. Our results indicate that XCQ is a potent natural product that could be a therapeutic strategy for constipation.
PubMed: 38399368
DOI: 10.3390/ph17020153 -
The Science of the Total Environment Apr 2024Biofilms, constituting over 95 % of the biomass in drinking water distribution systems, form an ecosystem impacting both the aesthetic and microbiological quality of...
Biofilms, constituting over 95 % of the biomass in drinking water distribution systems, form an ecosystem impacting both the aesthetic and microbiological quality of water. This study investigates the microbiome of biofilms within a real-scale drinking water distribution system in eastern Spain, utilizing amplicon-based metagenomics. Forty-one biofilm samples underwent processing and sequencing to analyze both bacterial and eukaryotic microbiomes, with an assessment of active biomass. Genus-level analysis revealed considerable heterogeneity, with Desulfovibrio, Ralstonia, Bradyrhizobium, Methylocystis, and Bacillus identified as predominant genera. Notably, bacteria associated with corrosion processes, including Desulfovibrio, Sulfuricella, Hyphomicrobium, and Methylobacterium, were prevalent. Potentially pathogenic bacteria such as Helicobacter, Pseudomonas, and Legionella were also detected. Among protozoa, Opisthokonta and Archaeplastida were the most abundant groups in biofilm samples, with potential pathogenic eukaryotes (Acanthamoeba, Naegleria, Blastocystis) identified. Interestingly, no direct correlation between microbiota composition and pipe materials was observed. The study suggests that the usual concentration of free chlorine in bulk water proved insufficient to prevent the presence of undesirable bacteria and protozoa in biofilms, which exhibited a high concentration of active biomass.
Topics: Water Quality; Drinking Water; Microbiota; Bacteria; Biofilms; Water Supply; Water Microbiology
PubMed: 38382601
DOI: 10.1016/j.scitotenv.2024.171086