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Osteoarthritis and Cartilage Dec 2021There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship.
OBJECTIVE
There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship.
METHOD
This study utilized large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and OA risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for OA. Comprehensively sensitive analyses were performed to validate the robustness of results and novel multivariable MR analyses were further conducted to ensure the independence of causal association. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. Finally, enrichment analyses were used to investigate the biofunction.
RESULTS
After correction, three microbial taxa were identified to be causally associated with diverse joint OA (P < 0.100), namely Methanobacteriaceae family for knee OA (P = 0.043) and any OA (P = 0.028), Desulfovibrionales order for knee OA (P = 0.045) and Ruminiclostridium5 genus for knee OA (P = 0.063). In addition, we also identified five suggestive microbial taxa that were significant with three different methods under the nominal significance (P < 0.05). Sensitive analysis excluded the influence of heterogeneity and horizontal pleiotropy and multivariable MR analysis ruled out the possibility of horizontal pleiotropy of BMI. GO enrichment analysis illustrates the protective mechanism of the identified taxa against OA.
CONCLUSIONS
This study found that several microbial taxa were causally associated with diverse joint OA. The results enhanced our understanding of gut microbiota in the pathology of OA.
Topics: Causality; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteoarthritis
PubMed: 34425228
DOI: 10.1016/j.joca.2021.08.003 -
The American Journal of Gastroenterology Dec 2022Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome...
INTRODUCTION
Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes.
METHODS
IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases.
RESULTS
IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D.
DISCUSSION
Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.
Topics: Humans; Irritable Bowel Syndrome; Hydrogen Sulfide; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Bacteria
PubMed: 36114762
DOI: 10.14309/ajg.0000000000001997 -
Nature Apr 2017Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal...
Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)-the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution.
Topics: Animals; Belgium; Carnivory; Caves; DNA, Ancient; Dental Calculus; Diet; Enterocytozoon; Food Preferences; Genome, Bacterial; Health; History, Ancient; Humans; Intestines; Meat; Methanobrevibacter; Mouth; Neanderthals; Pan troglodytes; Penicillium; Perissodactyla; Sheep; Spain; Stomach; Symbiosis; Time Factors; Vegetarians
PubMed: 28273061
DOI: 10.1038/nature21674 -
Nature Jun 2021Loss of gut microbial diversity in industrial populations is associated with chronic diseases, underscoring the importance of studying our ancestral gut microbiome....
Loss of gut microbial diversity in industrial populations is associated with chronic diseases, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.
Topics: Anti-Bacterial Agents; Bacteria; Biodiversity; Biological Evolution; Chronic Disease; Developed Countries; Developing Countries; Diet, Western; Feces; Gastrointestinal Microbiome; Genome, Bacterial; History, Ancient; Host Microbial Interactions; Humans; Industrial Development; Methanobrevibacter; Mexico; Sedentary Behavior; Southwestern United States; Species Specificity; Symbiosis
PubMed: 33981035
DOI: 10.1038/s41586-021-03532-0 -
PLoS Computational Biology Dec 2022Tree ensemble machine learning models are increasingly used in microbiome science as they are compatible with the compositional, high-dimensional, and sparse structure...
Tree ensemble machine learning models are increasingly used in microbiome science as they are compatible with the compositional, high-dimensional, and sparse structure of sequence-based microbiome data. While such models are often good at predicting phenotypes based on microbiome data, they only yield limited insights into how microbial taxa may be associated. We developed endoR, a method to interpret tree ensemble models. First, endoR simplifies the fitted model into a decision ensemble. Then, it extracts information on the importance of individual features and their pairwise interactions, displaying them as an interpretable network. Both the endoR network and importance scores provide insights into how features, and interactions between them, contribute to the predictive performance of the fitted model. Adjustable regularization and bootstrapping help reduce the complexity and ensure that only essential parts of the model are retained. We assessed endoR on both simulated and real metagenomic data. We found endoR to have comparable accuracy to other common approaches while easing and enhancing model interpretation. Using endoR, we also confirmed published results on gut microbiome differences between cirrhotic and healthy individuals. Finally, we utilized endoR to explore associations between human gut methanogens and microbiome components. Indeed, these hydrogen consumers are expected to interact with fermenting bacteria in a complex syntrophic network. Specifically, we analyzed a global metagenome dataset of 2203 individuals and confirmed the previously reported association between Methanobacteriaceae and Christensenellales. Additionally, we observed that Methanobacteriaceae are associated with a network of hydrogen-producing bacteria. Our method accurately captures how tree ensembles use features and interactions between them to predict a response. As demonstrated by our applications, the resultant visualizations and summary outputs facilitate model interpretation and enable the generation of novel hypotheses about complex systems.
Topics: Humans; Bacteria; Gastrointestinal Microbiome; Machine Learning; Metagenome; Microbiota
PubMed: 36516158
DOI: 10.1371/journal.pcbi.1010714 -
The Journal of General Physiology Apr 2017Regulator of conduction of K (RCK) domains are ubiquitous regulators of channel and transporter activity in prokaryotes and eukaryotes. In humans, RCK domains form an... (Review)
Review
Regulator of conduction of K (RCK) domains are ubiquitous regulators of channel and transporter activity in prokaryotes and eukaryotes. In humans, RCK domains form an integral component of large-conductance calcium-activated K channels (BK channels), key modulators of nerve, muscle, and endocrine cell function. In this review, we explore how the study of RCK domains in bacterial and human channels has contributed to our understanding of the structural basis of channel function. This knowledge will be critical in identifying mechanisms that underlie BK channelopathies that lead to epilepsy and other diseases, as well as regions of the channel that might be successfully targeted to treat such diseases.
Topics: Animals; Archaeal Proteins; Humans; Ion Channel Gating; Large-Conductance Calcium-Activated Potassium Channels; Methanobacterium; Potassium Channels; Protein Domains
PubMed: 28246116
DOI: 10.1085/jgp.201611726 -
Biochimica Et Biophysica Acta Aug 2016Life arose in a world without oxygen and the first organisms were anaerobes. Here we investigate the gene repertoire of the prokaryote common ancestor, estimating which... (Review)
Review
Life arose in a world without oxygen and the first organisms were anaerobes. Here we investigate the gene repertoire of the prokaryote common ancestor, estimating which genes it contained and to which lineages of modern prokaryotes it was most similar in terms of gene content. Using a phylogenetic approach we found that among trees for all 8779 protein families shared between 134 archaea and 1847 bacterial genomes, only 1045 have sequences from at least two bacterial and two archaeal groups and retain the ancestral archaeal-bacterial split. Among those, the genes shared by anaerobes were identified as candidate genes for the prokaryote common ancestor, which lived in anaerobic environments. We find that these anaerobic prokaryote common ancestor genes are today most frequently distributed among methanogens and clostridia, strict anaerobes that live from low free energy changes near the thermodynamic limit of life. The anaerobic families encompass genes for bifunctional acetyl-CoA-synthase/CO-dehydrogenase, heterodisulfide reductase subunits C and A, ferredoxins, and several subunits of the Mrp-antiporter/hydrogenase family, in addition to numerous S-adenosyl methionine (SAM) dependent methyltransferases. The data indicate a major role for methyl groups in the metabolism of the prokaryote common ancestor. The data furthermore indicate that the prokaryote ancestor possessed a rotor stator ATP synthase, but lacked cytochromes and quinones as well as identifiable redox-dependent ion pumping complexes. The prokaryote ancestor did possess, however, an Mrp-type H(+)/Na(+) antiporter complex, capable of transducing geochemical pH gradients into biologically more stable Na(+)-gradients. The findings implicate a hydrothermal, autotrophic, and methyl-dependent origin of life. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
Topics: Anaerobiosis; Archaea; Archaeal Proteins; Bacterial Proteins; Biological Evolution; Clostridiales; Coenzyme A Ligases; Ferredoxins; Hydrogenase; Metabolic Networks and Pathways; Methanobacteriaceae; Methyltransferases; Molecular Sequence Annotation; Origin of Life; Phylogeny; Protein Biosynthesis; Ribosomes
PubMed: 27150504
DOI: 10.1016/j.bbabio.2016.04.284 -
Clinical and Experimental Rheumatology Jan 2024To assess whether there is a bidirectional causal relationship between the composition of gut microbiota and rheumatoid arthritis (RA), and to identify specific...
OBJECTIVES
To assess whether there is a bidirectional causal relationship between the composition of gut microbiota and rheumatoid arthritis (RA), and to identify specific pathogenic bacterial taxa via the Mendelian randomisation (MR) analysis.
METHODS
We acquired single nucleotide polymorphisms (SNPs) associated with the composition of gut microbiota (n=18,340) and with RA (n=331,313) from publicly available genome-wide association studies (GWAS). The genome-wide threshold was 1 × 10-5 in the forward MR analysis and was 5 × 10-8 in the reverse MR analysis. Inverse variance weighted (IVW) was the main method to analyse causality, and MR results were verified by several sensitivity analyses including weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO).
RESULTS
The IVW method suggested that eight taxa were positively correlated with RA, including: MollicutesRF9 (pIVW <0.01), Alphaproteobacteria (pIVW <0.01), Betaproteobacteria (p IVW =0.04), Bacteroidaceae (pIVW <0.01), Adlercreutzia (pIVW <0.01), Bacteroides (pIVW <0.01), Butyricimonas (p IVW =0.03) and Holdemanella (pIVW =0.03). Six bacterial taxa were negatively correlated with RA, including Desulfovibrionales (pIVW = 0.01), Methanobacteriales (pIVW <0.01), Methanobacteria (PIVW <0.01), Desulfovibrionaceae (pIVW <0.01), Methanobacteriaceae (pIVW <0.01) and Butyrivibrio (pIVW =0.02). Heterogeneity (p>0.05) and pleiotropy (p>0.05) analysis confirmed the robustness of the MR results.
CONCLUSIONS
We identified some specific bacterial taxa that were causally associated with the risk of RA, providing new insights into prevention and diagnosis of RA.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Arthritis, Rheumatoid; Polymorphism, Single Nucleotide
PubMed: 37812479
DOI: 10.55563/clinexprheumatol/p9ig7c -
Journal of the Royal Society, Interface Jan 2015This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions... (Review)
Review
This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions to explore the Moon and Mars. Compared with anticipated non-biological approaches, it is determined that for 916 day Martian missions: 205 days of high-quality methane and oxygen Mars bioproduction with Methanobacterium thermoautotrophicum can reduce the mass of a Martian fuel-manufacture plant by 56%; 496 days of biomass generation with Arthrospira platensis and Arthrospira maxima on Mars can decrease the shipped wet-food mixed-menu mass for a Mars stay and a one-way voyage by 38%; 202 days of Mars polyhydroxybutyrate synthesis with Cupriavidus necator can lower the shipped mass to three-dimensional print a 120 m(3) six-person habitat by 85% and a few days of acetaminophen production with engineered Synechocystis sp. PCC 6803 can completely replenish expired or irradiated stocks of the pharmaceutical, thereby providing independence from unmanned resupply spacecraft that take up to 210 days to arrive. Analogous outcomes are included for lunar missions. Because of the benign assumptions involved, the results provide a glimpse of the intriguing potential of 'space synthetic biology', and help focus related efforts for immediate, near-term impact.
Topics: Acetaminophen; Biomass; Extraterrestrial Environment; Food Supply; Humans; Hydroxybutyrates; Methane; Methanobacterium; Moon; Nitrous Oxide; Oxygen; Photosynthesis; Plants; Polyesters; Space Flight; Spacecraft; Spirulina; Synechocystis; Synthetic Biology
PubMed: 25376875
DOI: 10.1098/rsif.2014.0715 -
Microbial Biotechnology Jan 2023Nanoparticles (NPs) supplementation to biodigesters improves the digestibility of biowaste and the generation of biogas. This study investigates the impact of innovative...
Nanoparticles (NPs) supplementation to biodigesters improves the digestibility of biowaste and the generation of biogas. This study investigates the impact of innovative nanoadditives on the microbiome of biodigesters. Fresh cow manure was anaerobically incubated in a water bath under mesophilic conditions for 30 days. Three different NPs (zinc ferrite, zinc ferrite with 10% carbon nanotubes and zinc ferrite with 10% C76 fullerene) were separately supplemented to the biodigesters at the beginning of the incubation period. Methane and hydrogen production were monitored daily. Manure samples were collected from the digesters at different time points and the microbial communities inside the biodigesters were investigated via real-time PCR and 16 S rRNA gene amplicon-sequencing. The results indicate that zinc ferrite NPs enhanced biogas production the most. The microbial community was significantly affected by NPs addition in terms of archaeal and bacterial 16 S rRNAgene copy numbers. The three ZF formulations NPs augmented the abundance of members within the hydrogenotrophic methanogenic phyla Methanobacteriaceae. While Methanomassiliicoccacaea were enriched in ZF/C76 supplemented biodigester due to a significant increase in hydrogen partial pressure, probably caused by the enrichment of Spirochaetaceae (genus Treponema). Overall, NPs supplementation significantly enriched acetate-producing members within Hungateiclostridiaceae in ZF/CNTs, Dysgonomonadaceae in ZF and Spirochaetaceae ZF/C76 biodigesters.
Topics: Animals; Cattle; Female; Bioreactors; Nanotubes, Carbon; Biofuels; Manure; Anaerobiosis; Microbiota; Methane; RNA, Ribosomal, 16S
PubMed: 36415905
DOI: 10.1111/1751-7915.14173