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Proceedings of the National Academy of... Aug 2013Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass... (Comparative Study)
Comparative Study
Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage's substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.
Topics: Animals; Bromodeoxyuridine; Chondroitin Sulfates; DNA Primers; DNA Transposable Elements; Desulfovibrio; Diet; Dietary Supplements; Feces; Gas Chromatography-Mass Spectrometry; Gastrointestinal Tract; Genetic Vectors; Humans; Hydrogen Sulfide; Mass Spectrometry; Mice; Mutagenesis; Sequence Analysis, DNA; Species Specificity
PubMed: 23898195
DOI: 10.1073/pnas.1312524110 -
Cells Apr 2023Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as...
Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as and . The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing, analyzed α- (Chao1 and Shannon indices) and β-diversity (Bray-Curtis dissimilarity), and conducted linear discriminant analysis (LDA) effect size (LEfSe) analysis. Neither α- nor β-diversity differed significantly between MDD and controls. , , , , and were significantly enriched in MDD, while Gracillibacteraceae family, , and , , , , and were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of , which is depleted in six different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients, with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of may be a more universal biomarker of MDD that may contribute to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.
Topics: Humans; Depressive Disorder, Major; Gastrointestinal Microbiome; Ruminococcus; Lipopolysaccharides; Southeast Asian People; Biomarkers
PubMed: 37174640
DOI: 10.3390/cells12091240 -
Gut Microbes 2023We report the first use of constraint-based microbial community modeling on a single individual with episodic inflammation of the gastrointestinal tract, who has a well...
We report the first use of constraint-based microbial community modeling on a single individual with episodic inflammation of the gastrointestinal tract, who has a well documented set of colonic inflammatory biomarkers, as well as metagenomically-sequenced fecal time series covering seven dates over 16 months. Between the first two time steps the individual was treated with both steroids and antibiotics. Our methodology enabled us to identify numerous time-correlated microbial species and metabolites. We found that the individual's dynamical microbial ecology in the disease state led to time-varying overproduction, compared to healthy controls, of more than 24 biologically important metabolites, including methane, thiamine, formaldehyde, trimethylamine N-oxide, folic acid, serotonin, histamine, and tryptamine. The microbe-metabolite contribution analysis revealed that some species changed metabolic pathways according to the inflammation phases. At the first time point, characterized by the highest levels of serum (complex reactive protein) and fecal (calprotectin) inflammation biomarkers, they produced L-serine or formate. The production of the compounds, through a cascade effect, was mediated by the interaction with pathogenic strains and . We integrated the microbial community metabolic models of each time point with a male whole-body, organ-resolved model of human metabolism to track the metabolic consequences of dysbiosis at different body sites. The presence of in the gut microbiome influenced the sulfur metabolism with a domino effect affecting the liver. These results revealed large longitudinal variations in an individual's gut microbiome ecology and metabolite production, potentially impacting other organs in the body. Future simulations with more time points from an individual could permit us to assess how external drivers, such as diet change or medical interventions, drive microbial community dynamics.
Topics: Humans; Male; Gastrointestinal Microbiome; Microbiota; Inflammation; Liver; Anti-Bacterial Agents; Escherichia coli
PubMed: 37438876
DOI: 10.1080/19490976.2023.2226921 -
Clinical and Translational Medicine Jun 2022Due to the increasing ageing population, neurocognitive disorders (NCDs) have been a global public health issue, and its prevention and early diagnosis are crucial. Our...
BACKGROUND
Due to the increasing ageing population, neurocognitive disorders (NCDs) have been a global public health issue, and its prevention and early diagnosis are crucial. Our previous study demonstrated that there is a significant correlation between specific populations and NCDs, but the biological characteristics of the vulnerable group predispose to NCDs are unclear. The purpose of this study is to investigate the predictors for the vulnerable group by a multi-omics analysis.
METHODS
Multi-omics approaches, including metagenomics, metabolomic and proteomic, were used to detect gut microbiota, faecal metabolites and urine exosome of 8 normal controls and 13 vulnerable elders after a rigorous screening of 400 elders in Macao. The multi-omics data were analysed using R and Bioconductor. The two-sided Wilcoxon's rank-sum test, Kruskal-Wallis rank sum test and the linear discriminant analysis effective size were applied to investigate characterized features. Moreover, a 2-year follow-up was conducted to evaluate cognitive function change of the elderly.
RESULTS
Compared with the control elders, the metagenomics of gut microbiota showed that Ruminococcus gnavus, Lachnospira eligens, Escherichia coli and Desulfovibrio piger were increased significantly in the vulnerable group. Carboxylates, like alpha-ketoglutaric acid and d-saccharic acid, and levels of vitamins had obvious differences in the faecal metabolites. There was a distinct decrease in the expression of eukaryotic translation initiation factor 2 subunit 1 (eIF2α) and amine oxidase A (MAO-A) according to the proteomic results of the urine exosomes. Moreover, the compound annual growth rate of neurocognitive scores was notably decreased in vulnerable elders.
CONCLUSIONS
The multi-omics characteristics of disturbed glyoxylate and dicarboxylate metabolism (bacteria), vitamin digestion and absorption and tricarboxylic acid cycle in vulnerable elders can serve as predictors of NCDs risk among the elderly of Macao. Intervention with them may be effective therapeutic approaches for NCDs, and the underlying mechanisms merit further exploration.
Topics: Aged; Gastrointestinal Microbiome; Humans; Macau; Metagenomics; Neurocognitive Disorders; Proteomics
PubMed: 35696554
DOI: 10.1002/ctm2.909 -
Frontiers in Microbiology 2021(captivity in zoos) is regarded as an important form of conservation for endangered animals. Many studies have compared differences in the gut microbiome between...
(captivity in zoos) is regarded as an important form of conservation for endangered animals. Many studies have compared differences in the gut microbiome between captive and wild animals, but few have explained those differences at the functional level due to the limited amount of 16S rRNA data. Here, we compared the gut microbiome of captive and wild , whose high degree of dietary specificity makes it a good subject to observe the effects of the captive environment on their gut microbiome, by performing a metagenome-wide association study (MWAS). The Chao1 index was significantly higher in the captive cohort than in the wild cohort, and the Shannon index of captive was higher than that of the wild cohort but the difference was not significant. A significantly increased ratio of /, which revealed an increased ability to digest simple carbohydrates, was found in the captive cohort. A significant decrease in the abundance of Firmicutes and enrichment of genes related to the pentose phosphate pathway were noted in the captive cohort, indicating a decreased ability of captive monkeys to digest fiber. Additionally, genes required for glutamate biosynthesis were also significantly more abundant in the captive cohort than in the wild cohort. These changes in the gut microbiome correspond to changes in the composition of the diet in captive animals, which has more simple carbohydrates and less crude fiber and protein than the diet of the wild animals. In addition, more unique bacteria in captive were involved in antibiotic resistance () and diarrhea (), and in the prevention of diarrhea () caused by . Accordingly, our data reveal the cause-and-effect relationships between changes in the exact dietary composition and changes in the gut microbiome on both the structural and functional levels by comparing of captive and wild .
PubMed: 34950117
DOI: 10.3389/fmicb.2021.763022 -
Digestive Diseases and Sciences Feb 2024We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (HS)-producing...
BACKGROUND
We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (HS)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii.
AIMS
In this study, we investigate the effects of increased methanogens or HS producers on stool phenotypes in rat models.
METHODS
Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase HS producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples.
RESULTS
In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool HS production. 16S sequencing revealed stool microbiota alterations in rats gavaged with HS producers, with higher relative abundance (RA) of other HS producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats.
CONCLUSIONS
These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with HS producers D. piger or F. varium results in increased colonization with other HS producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and HS producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.
Topics: Humans; Adult; Rats; Animals; Irritable Bowel Syndrome; Hydrogen Sulfide; Methane; RNA, Ribosomal, 16S; Rats, Sprague-Dawley; Constipation; Diarrhea; Models, Animal; Lovastatin
PubMed: 38060167
DOI: 10.1007/s10620-023-08197-5 -
Biomolecules Jun 2020A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate...
A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate reduction (APS reductase and dissimilatory sulfite reductase) in cell-free extracts of sulphate-reducing bacteria (SRB) from various biotopes was performed. The material for the study represented different strains of SRB from various ecotopes. Microbiological (isolation and cultivation), biochemical (free cell extract preparation) and chemical (enzyme activity determination) methods served in defining kinetic characteristics of SRB enzymes. The determined affinity data for substrates (i.e., sulfite) were 10 times higher for SRB strains isolated from environmental (soil) ecotopes than for strains from the human intestine. The maximum rate of APS reductase reached 0.282-0.862 µmol/min×mg of protein that is only 10 to 28% higher than similar initial values. The maximum rate of sulfite reductase for corrosive relevant collection strains and SRB strains isolated from heating systems were increased by 3 to 10 times. A completely different picture was found for the intestinal SRB V in the strains Desulfovibrio piger Vib-7 (0.67 µmol/min × mg protein) and Desulfomicrobium orale Rod-9 (0.45 µmol/min × mg protein). The determinant in the cluster distribution of SRB strains is the activity of the terminal enzyme of dissimilatory sulfate reduction-sulfite reductase, but not APS reductase. The data obtained from the activity of sulfate reduction enzymes indicated the adaptive plasticity of SRB strains that is manifested in the change in enzymatic activity.
Topics: Adenosine Phosphosulfate; Biodegradation, Environmental; Desulfovibrio desulfuricans; Desulfovibrio vulgaris; Hydrogen Sulfide; Oxidoreductases Acting on Sulfur Group Donors
PubMed: 32560561
DOI: 10.3390/biom10060921 -
Frontiers in Microbiology 2024Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established...
Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established that an imbalance in the composition of gut microbes, termed microbial dysbiosis, can initiate the progression of various diseases through the intricate interplay between gut microbiota and the host. However, the precise nature of the causal link between gut microbiota and hypertrophic scarring remains uncertain. In this study, after compiling summary data from genome-wide association studies (GWAS) involving 418 instances of gut microbiota and hypertrophic scarring, we conducted a bidirectional Mendelian randomization (MR) to investigate the potential existence of a causal relationship between gut microbiota and the development of hypertrophic scar and to discern the directionality of causation. By utilizing MR analysis, we identified seven causal associations between gut microbiome and hypertrophic scarring, involving one positive and six negative causal directions. Among them, , , , , , and act as protective factors against hypertrophic scarring, while suggests a potential role as a risk factor for hypertrophic scars. Additionally, sensitivity analyses of these results revealed no indications of heterogeneity or pleiotropy. The findings of our MR study suggest a potential causative link between gut microbiota and hypertrophic scarring, opening up new ways for future mechanistic research and the exploration of nanobiotechnology therapies for skin disorders.
PubMed: 38577682
DOI: 10.3389/fmicb.2024.1345717 -
Microorganisms Aug 2021This study was conducted to compare the infection heterogeneity and cecal microbiota in chicks infected by . Forty-eight 8-d-old female Arbor Acres chicks were...
This study was conducted to compare the infection heterogeneity and cecal microbiota in chicks infected by . Forty-eight 8-d-old female Arbor Acres chicks were challenged with and euthanized 24 h later. The eight chicks with the highest tissue loads were assigned to group S (-susceptible), and the eight chicks with the lowest tissue loads were assigned to group R (-resistant). Chicks in group S showed a higher liver index ( < 0.05), obvious liver lesions, and an decreasing trend for the villus height-to-crypt depth ratio ( < 0.10), compared with those in group R. Gene expression of , , and was higher, whereas that of and was lower ( < 0.05), in chicks of group R relative to those in group S. Separation of the cecal microbial community structure has been found between the two groups. The -susceptible chicks showed higher abundance of pathogenic bacteria ( and ) in their cecal, while was enriched in the cecal of -resistant chicks. In summary, chicks showed heterogeneous responses to infection. Enhanced intestinal barrier function and cecal microbiota structure, especially a higher abundance of , may help chicks resist invasion.
PubMed: 34442784
DOI: 10.3390/microorganisms9081705 -
Frontiers in Cellular and Infection... 2020Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome...
Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome composition in relation to type 2 diabetes (T2D) in Africans. Here, we describe the profile of the gut microbiome in non-diabetic adults (controls) and investigate the association between gut microbiota and T2D in urban West Africans. Gut microbiota composition was determined in 291 Nigerians (98 cases, 193 controls) using fecal 16S V4 rRNA gene sequencing done on the Illumina MiSeq platform. Data analysis of operational taxonomic units (OTU) was conducted to describe microbiome composition and identify differences between T2D and controls. The most abundant phyla were , and . , and were significantly lower in cases than controls ( < 0.001). Feature selection analysis identified a panel of 18 OTUs enriched in cases that included . A panel of 17 OTUs that was enriched in the controls included , and . OTUs with strain-level annotation showing the largest fold-change included (logFC = -3.1; = 4.2 × 10), (logFC = -2.5; = 0.005), (logFC = -1.76; = 0.01), all lower in cases. These findings are notable because supplementation with and has been shown to improve hyperglycemia and reduce insulin resistance in murine models. This first investigation of gut microbiome and diabetes in urban Africans shows that T2D is associated with compositional changes in gut microbiota highlighting the possibility of developing strategies to improve glucose control by modifying bacterial composition in the gut.
Topics: Actinobacteria; Bacteroidetes; Black People; Case-Control Studies; Diabetes Mellitus, Type 2; Dysbiosis; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Nigeria; Urban Health
PubMed: 32158702
DOI: 10.3389/fcimb.2020.00063