-
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 -
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 -
Aging Cell Dec 2023Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a...
Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.
Topics: Humans; Aged; Gastrointestinal Microbiome; China; Metabolome; Aging; Biomarkers; Kidney
PubMed: 38015106
DOI: 10.1111/acel.14028 -
Gut Microbes Dec 2023Methanogens, reductive acetogens and sulfate-reducing bacteria play an important role in disposing of hydrogen in gut ecosystems. However, how they interact with each...
Methanogens, reductive acetogens and sulfate-reducing bacteria play an important role in disposing of hydrogen in gut ecosystems. However, how they interact with each other remains largely unknown. This study cocultured (reductive acetogen), (sulfate reducer) and (methanogen). Results revealed that these three species coexisted and did not compete for hydrogen in the early phase of incubations. Sulfate reduction was not affected by and . inhibited the growth of and after 10 h incubations, and the inhibition on was associated with increased sulfide concentration. Remarkably, growth lag phase was shortened by coculturing with and . Formate was rapidly used by under high acetate concentration. Overall, these findings indicated that the interactions of the hydrogenotrophic microbes are condition-dependent, suggesting their interactions may vary in gut ecosystems.
Topics: Methanobrevibacter; Ecosystem; Gastrointestinal Microbiome; Hydrogen; Sulfates
PubMed: 37753963
DOI: 10.1080/19490976.2023.2261784 -
Scientific Reports Aug 2023Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate...
Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate reduction and may create a synergistic effect. Here, we report NADH and NADPH peroxidase activities from intestinal SRB Desulfomicrobium orale and Desulfovibrio piger. We sought to compare enzymatic activities under the influence of various temperature and pH regimes, as well as to carry out kinetic analyses of enzymatic reaction rates, maximum amounts of the reaction product, reaction times, maximum rates of the enzyme reactions, and Michaelis constants in cell-free extracts of intestinal SRB, D. piger Vib-7, and D. orale Rod-9, collected from exponential and stationary growth phases. The optimal temperature (35 °C) and pH (7.0) for both enzyme's activity were determined. The difference in trends of Michaelis constants (K) during exponential and stationary phases are noticeable between D. piger Vib-7 and D. orale Rod-9; D. orale Rod-9 showed much higher K (the exception is NADH peroxidase of D. piger Vib-7: 1.42 ± 0.11 mM) during the both monitored phases. Studies of the NADH and NADPH peroxidases-as putative antioxidant defense systems of intestinal SRB and detailed data on the kinetic properties of this enzyme, as expressed by the decomposition of hydrogen peroxide-could be important for clarifying evolutionary mechanisms of antioxidant defense systems, their etiological role in the process of dissimilatory sulfate reduction, and their possible role in the development of bowel diseases.
Topics: Animals; Humans; Antioxidants; NAD; NADP; Cell Extracts; Desulfovibrio; Peroxidases; Defense Mechanisms; Sulfates
PubMed: 37626119
DOI: 10.1038/s41598-023-41185-3 -
Nature Aug 2023The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease. The development of next-generation probiotics is a...
The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease. The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations. Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: NCT03728868 ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.
Topics: Animals; Humans; Mice; Butyrates; Gastrointestinal Microbiome; Oxygen; Probiotics; Aerobiosis; Faecalibacterium prausnitzii; Symbiosis; Biotechnology
PubMed: 37532933
DOI: 10.1038/s41586-023-06378-w -
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 -
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 -
PLoS Biology May 2023In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We...
In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of C. difficile to clinically relevant antibiotics using bottom-up assembly of human gut communities. We identify 2 classes of microbial interactions that alter C. difficile's antibiotic susceptibility: interactions resulting in increased ability of C. difficile to grow at high antibiotic concentrations (rare) and interactions resulting in C. difficile growth enhancement at low antibiotic concentrations (common). Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut species Desulfovibrio piger increases the minimum inhibitory concentration (MIC) of metronidazole for C. difficile. Competition with species that display higher sensitivity to the antibiotic than C. difficile leads to enhanced growth of C. difficile at low antibiotic concentrations due to competitive release. A dynamic computational model identifies the ecological principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shaping C. difficile's response to antibiotics, which could inform therapeutic interventions.
Topics: Humans; Anti-Bacterial Agents; Gastrointestinal Microbiome; Clostridioides difficile; Clostridioides; Clostridium Infections
PubMed: 37167201
DOI: 10.1371/journal.pbio.3002100 -
International Journal of Molecular... Nov 2022Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these...
Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including (, , , ), , and a sulfur reducer increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.
Topics: Child; Humans; Autistic Disorder; RNA, Ribosomal, 16S; Autism Spectrum Disorder; Microbiota; Metagenomics; Oxidative Stress; Sulfur
PubMed: 36362265
DOI: 10.3390/ijms232113481