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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 -
Minerva Gastroenterology Dec 2021Gut microbiota plays a vital role in human health. The number of microorganisms inhabiting the gastrointestinal (GI) tract has been estimated to exceed 10. The dominant... (Review)
Review
Gut microbiota plays a vital role in human health. The number of microorganisms inhabiting the gastrointestinal (GI) tract has been estimated to exceed 10. The dominant genera in the human intestine are Firmicutes (more than 180 species of Lactobacillus), Actinobacteria (among others the Bifidobacteriae), Bacteroidetes (the most important is B. fragilis) and Proteobacteria (E. coli, Salmonella, Yersinia, Shigella, Vibrio, Haemophilus, etc.), but the composition of the flora varies individually, as well as in relation to factors such as host genetics, stress, diet, antibiotics and early childhood experiences. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGIDs), which has now been renamed disorders of gut-brain interaction, which affect a large number of people worldwide. It is characterized by abdominal pain and altered bowel habits in the absence of obvious anatomic or physiologic abnormalities. It poses a negative economic impact to the global health care system in addition to reducing the quality of life in patients. The pathophysiology of IBS is not fully understood. In IBS subjects gut microbiota relative to healthy controls was observed with an increase in Enterobacteriaceae, Ruminococcus, Clostridium, Dorea species and a decrease of Lactobacillus, Bifidobacterium, and Faecalibacterium species. IBS with diarrhea predominance (IBS-D) IBS with mixed bowel habits (IBS-M) share similarities in the microbial profile. Recent studies suggest that perturbations within "brain-gut-microbiota" axis may lead to IBS development. The aim of this review was to highlight the potential role of gut microbiota on pathophysiological mechanisms underlying IBS.
Topics: Child, Preschool; Diarrhea; Escherichia coli; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome; Quality of Life
PubMed: 34515452
DOI: 10.23736/S2724-5985.21.02923-5 -
Frontiers in Cellular and Infection... 2022Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial... (Review)
Review
Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of , , and and a decrease in genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including , , , and , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Mice; Microfilament Proteins; Nerve Tissue Proteins; Quality of Life
PubMed: 35846755
DOI: 10.3389/fcimb.2022.905841 -
Frontiers in Cellular and Infection... 2022Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal...
Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal relationship. To reveal the causal relationship between gut microbiota and cardiovascular protein levels in plasma, we estimated their causal effects using two-sample Mendelian randomization (MR) analysis. Sensitivity analysis was also performed to assess the robustness of our results. Genome-wide association study (GWAS) of microbiomes in the MiBioGen study included 211 bacterial taxa (18,473 individuals), and GWAS of 90 cardiovascular proteins included 30,931 individuals. There were 196 bacterial taxa from five levels available for analysis. The following 14 causal relationships were identified: phylum and carbohydrate antigen 125 (β = 0.289), order and CSF-1 (β = -0.211), genus and HSP-27 (β = 0.465), phylum and IL-8 (β = 0.274), order and KIM-1 (β = -0.499), class , genus , phylum and LEP (β = -0.219, β = -0.201, and β = -0.221), genus and NT-proBNP (β = 0.371), family and SRC (β = 0.191), order , phylum and TNF-R2 (β = 0.251 and β = 0.233), family and t-PA (β = 0.271), and class and VEGF-D (β = 0.390). Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. The results of the reverse MR analysis showed no reverse causality for any of the 13 gut microbes and 11 cardiovascular proteins. Mendelian randomization estimates provide strong evidence for a causal effect of gut microbiota-mediated alterations on cardiovascular protein expression.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Causality; Bacteria; Polymorphism, Single Nucleotide
PubMed: 36544908
DOI: 10.3389/fcimb.2022.1048519 -
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 -
Journal of Autoimmunity May 2023A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and...
BACKGROUND
A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and Vogt-Koyanagi-Harada disease (VKH). Integrated-analysis and subsequent validation of these results could be a potentially powerful way to understand the microbial signatures and their functions in these two uveitis entities.
METHODS
We integrated the sequencing data of our previous metagenomic studies on two major uveitis entities, BU and VKH as well as four other publicly available immune-mediated diseases datasets, including Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Crohn's disease (CD) and Ulcerative Colitis (UC). Alpha-diversity and beta-diversity analysis were used to compare the gut microbiome signatures between both uveitis entities and other immune-mediated diseases and healthy controls. Amino acid homology between microbial proteins and a uveitogenic peptide of the interphotoreceptor retinoid-binding protein (IRBP) was investigated using a similarity search in the NCBI protein BLAST program (BLASTP). Enzyme-linked Immunosorbent Assay (ELISA) was performed to evaluate the cross-reactive responses of experimental autoimmune uveitis (EAU)-derived lymphocytes and BU patients-derived peripheral blood mononuclear cells (PBMCs) against homologous peptides. The area under the curve (AUC) analysis was used to test the sensitivity and specificity of gut microbial biomarkers.
RESULTS
Depleted Dorea, Blautia, Coprococcus, Erysipelotrichaceae and Lachnospiraceae as well as enriched Bilophila and Stenotrophomonas were identified in BU patients. An enriched Alistipes along with a lower level of Dorea were observed in VKH patients. A peptide antigen (SteTDR) encoded by BU specifically enriched Stenotrophomonas was identified to share homology with IRBP. In vitro experiments showed that lymphocytes from EAU or PBMCs from BU patients reacted to this peptide antigen as shown by the production of IFN-γ and IL-17. Addition of the SteTDR peptide to the classical IRBP immunization protocol exacerbated EAU severity. Gut microbial marker profiles consisted of 24 species and 32 species respectively differentiated BU and VKH from each other as well as from the other four immune-mediated diseases and healthy controls. Protein annotation identified 148 and 119 specific microbial proteins associated with BU and VKH, respectively. For metabolic function analysis, 108 and 178 metabolic pathways were shown to be associated with BU and VKH, respectively.
CONCLUSIONS
Our study revealed specific gut microbial signatures and their potentially functional roles in BU and VKH pathogenesis that differ significantly from other immune-mediated diseases as well as healthy controls.
Topics: Humans; Uveomeningoencephalitic Syndrome; Leukocytes, Mononuclear; Gastrointestinal Microbiome; Uveitis; Behcet Syndrome
PubMed: 37208257
DOI: 10.1016/j.jaut.2023.103055 -
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 -
Ambio May 2023Mercury (Hg) is a chemical of health concern worldwide that is now being acted upon through the Minamata Convention. Operationalizing the Convention and tracking its... (Review)
Review
Mercury (Hg) is a chemical of health concern worldwide that is now being acted upon through the Minamata Convention. Operationalizing the Convention and tracking its effectiveness requires empathy of the diversity and variation of mercury exposure and risk in populations worldwide. As part of the health plenary for the 15th International Conference on Mercury as a Global Pollutant (ICMGP), this review paper details how scientific understandings have evolved over time, from tragic poisoning events in the mid-twentieth century to important epidemiological studies in the late-twentieth century in the Seychelles and Faroe Islands, the Arctic and Amazon. Entering the twenty-first century, studies on diverse source-exposure scenarios (e.g., ASGM, amalgams, contaminated sites, cosmetics, electronic waste) from across global regions have expanded understandings and exemplified the need to consider socio-environmental variables and local contexts when conducting health studies. We conclude with perspectives on next steps for mercury health research in the post-Minamata Convention era.
Topics: Humans; Arctic Regions; Denmark; Environmental Pollutants; Mercury; Environmental Exposure
PubMed: 36790578
DOI: 10.1007/s13280-023-01831-6 -
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 -
Advances in Nutrition (Bethesda, Md.) May 2020
Topics: Public Health
PubMed: 32419020
DOI: 10.1093/advances/nmaa002