Characteristic gut microbiota and metabolic changes in patients with pulmonary tuberculosis.
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ABSTRACT:
SUBMITTER: Wang S
PROVIDER: S-EPMC8719804 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:One-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls (p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group (p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.
| S-EPMC5698276 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a chronic endocrine and metabolic disease. Gut microbiota is closely related to many chronic diseases. In this study, we conducted a cross-sectional study and recruited 30 obese (OG) and 30 non-obese (NG) women with PCOS, 30 healthy women (NC) and 11 healthy but obese women (OC) as controls to investigate the characteristic gut microbiota and its metabolic functions in obese and non-obese patients with PCOS. The blood and non-menstrual faecal samples of all the participants were collected and analysed. As a result, the Hirsutism score, LH/FSH and serum T level in NG and OG both increased significantly compared with their controls (P < 0.05). High-throughput 16S rRNA gene sequencing revealed that the abundance and diversity of the gut microbiota changed in patients with PCOS. The linear discriminant analysis (LDA) indicated that Lactococcus was the characteristic gut microbiota in NG, while Coprococcus_2 in OG. Correlation heatmap analysis revealed that the sex hormones and insulin levels in human serum were closely related to the changes in the gut microbiota of NG and OG. Functional prediction analysis demonstrated that the citrate cycle pathway enriched both in NG and OG, and other 12 gut bacterial metabolic pathways enriched in NG. This study highlighted significant differences in the gut microbiota and predictive functions of obese and non-obese women with PCOS, thereby providing insights into the role and function of the gut microbiota that may contribute to the occurrence and development of PCOS in obese and non-obese women.
| S-EPMC6993273 | biostudies-literature
Project description:BackgroundThe relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood.MethodsTo identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB.FindingsCases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways.InterpretationTB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB.FundingEuropean & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases.
| S-EPMC8122180 | biostudies-literature
Project description:Patients with pulmonary tuberculosis (TB) undergoing anti-tuberculosis (anti-TB) treatment were previously reported to present gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been reported. Here, we conducted a follow-up study of 29 naive TB patients who received first-line anti-TB drug treatment; we collected their fecal samples at different time points, as well as 22 fecal samples from healthy subjects. Fungal ITS2 and bacterial 16S rRNA amplicon sequencing were used to analyze the effects of active TB and anti-TB treatment on the gut microbiota. We found that naive TB patients had bacterial and fungal dysbiosis with altered community composition and a decreased density of the transkingdom correlation network. Anti-TB drug treatment significantly decreased the diversity of bacteria and fungi with altered composition. Notably, we observed that the abundance of Purpureocillium lilacinum tended to decrease and Nakaseomyces spp. tended to increase in the anti-TB treatment, and all of them had increased proportions in the three TB groups compared with healthy subjects. We found that the fungal-bacterial transkingdom network was severely altered in TB patients after 2 months of treatment, and new fungal-enriched connections that were not observed in other groups after 6 months of treatment. This study provides the first detailed analysis of dysbiosis of the gut mycobiota due to active TB and anti-TB treatment. The results suggest that fungi play an important role in the balance of the gut microbiota and may be associated with the progression of TB, influencing the microbiota and immunity homeostasis in those receiving anti-TB treatment. IMPORTANCE Numerous studies have shown that the gut bacterial microbiota is altered in active TB patients and that anti-TB drugs have profound and long-term impacts. However, as an integral part of the microbiota, fungi have rarely been studied. The need to investigate both the bacterial and fungal microbiota, as well as the relationship between them is apparent. The significance of our study is in our examination of the changes in the bacterial and fungal microbiota simultaneously in both active TB and patients receiving anti-TB treatment. We found that fungi play an important role in the bacterial-fungal transkingdom network, especially during the anti-TB therapy. These findings underscore the importance of fungi in gut microbiota dysbiosis during active TB and anti-TB treatment processes. In addition, our findings suggest it is meaningful to research potential adjunctive therapies that reduce fungal expansion and increase commensal bacterial abundance after anti-TB treatment, which would help the recovery of TB patients.
| S-EPMC8672887 | biostudies-literature
Project description:Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.
| S-EPMC4847541 | biostudies-literature
Project description:This study aims to characterize the gut microbiota in depressed patients with bipolar disorder (BD) compared with healthy controls (HCs), to examine the effects of quetiapine treatment on the microbiota, and to explore the potential of microbiota as a biomarker for BD diagnosis and treatment outcome. Analysis of 16S-ribosomal RNA gene sequences reveals that gut microbial composition and diversity are significantly different between BD patients and HCs. Phylum Bacteroidetes and Firmicutes are the predominant bacterial communities in BD patients and HCs, respectively. Lower levels of butyrate-producing bacteria are observed in untreated patients. Microbial composition changes following quetiapine treatment in BD patients. Notably, 30 microbial markers are identified on a random forest model and achieve an area under the curve (AUC) of 0.81 between untreated patients and HCs. Ten microbial markers are identified with the AUC of 0.93 between responder and nonresponder patients. This study characterizes the gut microbiota in BD and is the first to evaluate microbial changes following quetiapine monotherapy. Gut microbiota-based biomarkers may be helpful in BD diagnosis and predicting treatment outcome, which need further validations.
| S-EPMC6662053 | biostudies-literature
Project description:BackgroundRoux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m2).MethodsDM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing.ResultsTwenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages.ConclusionsThis was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level.Trial registrationISRCTN53984585.
| S-EPMC8139007 | biostudies-literature
Project description:Cross talk occurs between the human gut and the lung through a gut-lung axis involving the gut microbiota. However, the signatures of the human gut microbiota after active Mycobacterium tuberculosis infection have not been fully understood. Here, we investigated changes in the gut microbiota in tuberculosis (TB) patients by shotgun sequencing the gut microbiomes of 31 healthy controls and 46 patients. We observed a dramatic changes in gut microbiota in tuberculosis patients as reflected by significant decreases in species number and microbial diversity. The gut microbiota of TB patients were mostly featured by the striking decrease of short-chain fatty acids (SCFAs)-producingbacteria as well as associated metabolic pathways. A classification model based on the abundance of three species, Haemophilus parainfluenzae, Roseburia inulinivorans, and Roseburia hominis, performed well for discriminating between healthy and diseased patients. Additionally, the healthy and diseased states can be distinguished by SNPs in the species of B. vulgatus. We present a comprehensive profile of changes in the microbiota in clinical TB patients. Our findings will shed light on the design of future diagnoses and treatments for M. tuberculosis infections.
| S-EPMC6456665 | biostudies-literature
Project description:The importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion trap time-of-flight multistage mass spectrometry (LC-MS/MS and LC/MSn-IT-TOF), four metabolites of triptolide (M1, M2, M3, and M4) were found in the intestinal contents of rats. M1 and M2, were isomeric monocarbonyl-hydroxyl-substituted metabolites with molecular weights of 390. M3 and M4 were isomeric dehydrogenated metabolites with molecular weights of 356. Among the four metabolites, the dehydrogenated metabolites (M3 and M4) were reported in the gut microbiota for the first time. The metabolic behaviors of triptolide in the gut microbiota and liver microsomes of rats were further compared. The monocarbonyl-hydroxyl-substituted metabolites (M1 and M2) were generated in both systems, and another monohydroxylated metabolite (M5) was found only in the liver microsomes. The combined results suggested that the metabolism of triptolide in the gut microbiota was specific, with two characteristic, dehydrogenated metabolites. This investigation might provide a theoretical basis for the elucidation of the metabolism mechanism of triptolide and guide its proper application in clinical administration.
| S-EPMC7037371 | biostudies-literature
Project description:The main objective of this study was to investigate the alterations in the gut microbiota (GM) of pulmonary fibrosis (PF) mice induced by bleomycin (BLM) with its underlying mechanisms. BLM was docked with the targets of TGF-β/SMAD and caspase-3 pathways using the molecular docking technique. HE staining and Masson staining were applied to observe the histopathological changes in the pulmonary tissues. Detection of the apoptotic signals was conducted by flow cytometry and TUNEL staining. The mRNA expression of targets involved in the TGF-β/SMAD and caspase-3 signaling pathways in lungs was determined by qPCR. Immunohistochemistry (IHC) assay was used to detect the expression levels of cleaved caspase-3 and BAX proteins in mice lung tissues. 16S rDNA sequencing analysis was used to investigate the changes of GM in the fecal samples of mice in each group. The results showed that the apoptosis rate of pulmonary cells in the BLM group distinctly increased, with the expression levels of crucial target pro-apoptotic gene caspase-3, BAX with the corresponding protein, cleaved caspase-3, BAX were apparently elevated. This was accompanied by a significant increase in pro-fibrotic targets level such as TGF-β, fibronectin, collagen I, and collagen III. The mechanisms of PF induced by BLM were related to apoptosis of lung tissue cells such as alveolar epithelial cells and destroyed alveolar structure and excessive production of extracellular matrix (ECM), which may be bound up with activating TGF-β/SMAD and caspase-3 pathways. As for the GM, it was found that, after BLM induced PF in mice, the micro ecological balance of the GM was destroyed; the distance of PCo1 and Pco2 was significantly elongated, and the relative abundance of some intestinal probiotics like Catenibacterium and Lactobacillus (L. johnsonii and L. gasseri) dramatically lowered while the relative abundance of Verrucomicrobiales and Enterobacteriales substantially increased. Therefore, GM changes associated with PF in mouse models induced by BLM and the concept of "gut-lung axis" might provide an optional therapeutic strategy for PF.
| S-EPMC9561135 | biostudies-literature