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PloS One 2023The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome...
BACKGROUND
The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients.
METHODS
We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions).
RESULTS
Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value.
CONCLUSIONS
We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues.
TRIAL REGISTRATION
Clinical Trial registration number: NCT00970801.
Topics: Humans; RNA, Ribosomal, 16S; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Lung Diseases; Lung; Microbiota; Nontuberculous Mycobacteria
PubMed: 37235629
DOI: 10.1371/journal.pone.0285143 -
Frontiers in Cellular and Infection... 2023Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the...
BACKGROUND
Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this potential causal relationship are still unclear. This study used two-sample Mendelian randomization (MR) to clarify the potential causal links.
METHODS
Summary-level Genome-Wide Association Studies (GWAS) statistical data for gut microbiota and NAFLD/NASH were obtained from MiBioGen and FinnGen respectively. The MR analyses were performed mainly using the inverse-variance weighted (IVW) method, with sensitivity analyses conducted to verify the robustness. Additionally, reverse MR analyses were performed to examine any potential reverse causal associations.
RESULTS
Our analysis, primarily based on the IVW method, strongly supports the existence of causal relationships between four microbial taxa and NAFLD, and four taxa with NASH. Specifically, associations were observed between Enterobacteriales ( =0.04), ( =0.04), ( =0.02), and ( =0.04) and increased risk of NAFLD. ( =0.03) and ( =0.04) could increase the risks of NASH while ( =0.04) and (=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in ( =0.007) and ( =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.
CONCLUSION
This study identified several specific gut microbiota that are causally related to NAFLD and NASH. Observations herein may provide promising theoretical groundwork for potential prevention and treatment strategies for NAFLD and its progression to NASH in future.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Clostridiaceae; Clostridiales
PubMed: 38106475
DOI: 10.3389/fcimb.2023.1294826 -
Nature Communications Apr 2023Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported,...
Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
Topics: Male; Humans; Female; Absorptiometry, Photon; Body Composition; Bone Density; Sarcopenia; Osteoporosis
PubMed: 37080991
DOI: 10.1038/s41467-023-37978-9 -
Frontiers in Cellular and Infection... 2023Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the...
INTRODUCTION
Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia.
METHODS
In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations.
RESULTS
Ten GM taxa were detected to have causal associations with insomnia. Among them, class , genus , genus , genus , genus , and order were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa.
CONCLUSION
It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.
Topics: Humans; Gastrointestinal Microbiome; Sleep Initiation and Maintenance Disorders; Mendelian Randomization Analysis; Central Nervous System; Clostridiaceae; Genome-Wide Association Study
PubMed: 38089822
DOI: 10.3389/fcimb.2023.1296417 -
Pathogens (Basel, Switzerland) Jul 2022is an anaerobic Gram-positive and spore-forming bacterium. The majority of strains produce two toxins, A and B, associated with the development of acute diarrhea... (Review)
Review
is an anaerobic Gram-positive and spore-forming bacterium. The majority of strains produce two toxins, A and B, associated with the development of acute diarrhea and/or colitis. In this review, two situations are distinguished: infection (CDI) and asymptomatic colonization (AC). The main objective of this review is to explore the available data related to the link between the gut microbiota and the development of CDI. The secondary aim is to provide more information on why some people colonized with toxigenic develop an infection while others show no signs of disease. Several factors, such as the use of antibiotics and proton pump inhibitors, hospitalization, and age, predispose individuals to colonization and/or infection. The gut microbiota of people with AC showed decreased abundances of , , , , , , and . The gut microbiota of people suffering from CDI showed reductions in the abundances of , , spp., spp., spp., spp., spp., spp., spp. and spp., in comparison with healthy people. Furthermore, increases in the abundances of and were associated with infection.
PubMed: 35890026
DOI: 10.3390/pathogens11070781 -
Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
Aging Sep 2023Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with...
BACKGROUND
Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
METHODS
We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
RESULTS
The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of , , , , and with GH, of (), (), , , and with PE, and of and with eclampsia, respectively.
CONCLUSIONS
This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Topics: Female; Pregnancy; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Mendelian Randomization Analysis
PubMed: 37698537
DOI: 10.18632/aging.205019 -
Biomolecules Aug 2021Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by... (Review)
Review
Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn overexposure on gut microbiota dysbiosis, which is known to contribute to neurodegeneration via secretion of neuroactive and proinflammatory metabolites. Therefore, in this review, we discuss the existing data on the impact of Mn exposure on gut microbiota biodiversity, bacterial metabolite production, and gut wall permeability regulating systemic levels. Recent data have demonstrated that Mn exposure may affect gut microbiota biodiversity by altering the abundance of Shiegella, Ruminococcus, Dorea, Fusicatenibacter, Roseburia, Parabacteroides, Bacteroidetes, Firmicutes, Ruminococcaceae, Streptococcaceae, and other bacterial phyla. A Mn-induced increase in Bacteroidetes abundance and a reduced Firmicutes/Bacteroidetes ratio may increase lipopolysaccharide levels. Moreover, in addition to increased systemic lipopolysaccharide (LPS) levels, Mn is capable of potentiating LPS neurotoxicity. Due to the high metabolic activity of intestinal microflora, Mn-induced perturbations in gut microbiota result in a significant alteration in the gut metabolome that has the potential to at least partially mediate the biological effects of Mn overexposure. At the same time, a recent study demonstrated that healthy microbiome transplantation alleviates Mn-induced neurotoxicity, which is indicative of the significant role of gut microflora in the cascade of Mn-mediated neurotoxicity. High doses of Mn may cause enterocyte toxicity and affect gut wall integrity through disruption of tight junctions. The resulting increase in gut wall permeability further promotes increased translocation of LPS and neuroactive bacterial metabolites to the systemic blood flow, ultimately gaining access to the brain and leading to neuroinflammation and neurotransmitter imbalance. Therefore, the existing data lead us to hypothesize that gut microbiota should be considered as a potential target of Mn toxicity, although more detailed studies are required to characterize the interplay between Mn exposure and the gut, as well as its role in the pathogenesis of neurodegeneration and other diseases.
Topics: Animals; Gastrointestinal Microbiome; Humans; Immunity; Manganese; Metabolome; Nerve Degeneration; Neurotoxins
PubMed: 34572505
DOI: 10.3390/biom11091292 -
BMC Pediatrics May 2023Childhood obesity is a serious public health concern that confers a greater risk of developing important comorbidities such as MetS and T2DM. Recent studies evidence...
BACKGROUND
Childhood obesity is a serious public health concern that confers a greater risk of developing important comorbidities such as MetS and T2DM. Recent studies evidence that gut microbiota may be a contributing factor; however, only few studies exist in school-age children. Understanding the potential role of gut microbiota in MetS and T2DM pathophysiology from early stages of life might contribute to innovative gut microbiome-based interventions that may improve public health. The main objective of the present study was to characterize and compare gut bacteria of T2DM and MetS children against control subjects and determine which microorganisms might be potentially related with cardiometabolic risk factors to propose gut microbial biomarkers that characterize these conditions for future development of pre-diagnostic tools.
RESULTS
Stool samples from 21 children with T2DM, 25 with MetS, and 20 controls (n = 66) were collected and processed to conduct 16S rDNA gene sequencing. α- and β-diversity were studied to detect microbial differences among studied groups. Spearman correlation was used to analyze possible associations between gut microbiota and cardiometabolic risk factors, and linear discriminant analyses (LDA) were conducted to determine potential gut bacterial biomarkers. T2DM and MetS showed significant changes in their gut microbiota at genus and family level. Read relative abundance of Faecalibacterium and Oscillospora was significantly higher in MetS and an increasing trend of Prevotella and Dorea was observed from the control group towards T2DM. Positive correlations were found between Prevotella, Dorea, Faecalibacterium, and Lactobacillus with hypertension, abdominal obesity, high glucose levels, and high triglyceride levels. LDA demonstrated the relevance of studying least abundant microbial communities to find specific microbial communities that were characteristic of each studied health condition.
CONCLUSIONS
Gut microbiota was different at family and genus taxonomic levels among controls, MetS, and T2DM study groups within children from 7 to 17 years old, and some communities seemed to be correlated with relevant subjects' metadata. LDA helped to find potential microbial biomarkers, providing new insights regarding pediatric gut microbiota and its possible use in the future development of gut microbiome-based predictive algorithms.
Topics: Humans; Child; Adolescent; Metabolic Syndrome; Gastrointestinal Microbiome; Pediatric Obesity; Diabetes Mellitus, Type 2; Bacteria; Biomarkers; RNA, Ribosomal, 16S
PubMed: 37138212
DOI: 10.1186/s12887-023-03983-6 -
Signal Transduction and Targeted Therapy Sep 2023The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool...
The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.
Topics: Humans; COVID-19 Vaccines; Gastrointestinal Microbiome; BNT162 Vaccine; Cohort Studies; COVID-19; SARS-CoV-2; Antibodies, Neutralizing
PubMed: 37743379
DOI: 10.1038/s41392-023-01629-8