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Frontiers in Molecular Biosciences 2022IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and...
IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. and levels were higher, while and levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by was closely related to the IgAN patients. Moreover, , and were characteristic bacteria enriched in IgAN patients. Spearman's correlation analysis found that and were positively correlated with urine protein-creatinine ratio, while showed a direct association with red blood cells in urine, and and were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by were enriched in IgAN patients. These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.
PubMed: 36090029
DOI: 10.3389/fmolb.2022.970723 -
Journal of Clinical Medicine Apr 2021Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity...
Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (, , , , and ) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, = 2 × 10). Five genes (, , , , and ) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
PubMed: 33920646
DOI: 10.3390/jcm10081749 -
Inflammatory Bowel Diseases May 2024The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal...
BACKGROUND
The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.
METHODS
Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies.
RESULTS
Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling.
CONCLUSIONS
This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.
PubMed: 38733623
DOI: 10.1093/ibd/izae080 -
Biomedicines May 2024The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on...
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with , , and others, while milder cases were linked to , , , and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.
PubMed: 38790958
DOI: 10.3390/biomedicines12050996 -
Nutrients Nov 2022(1) Background: Pregnancy-induced hypertension (PIH) is associated with obvious microbiota dysbiosis in the third trimester of pregnancy. However, the mechanisms behind...
(1) Background: Pregnancy-induced hypertension (PIH) is associated with obvious microbiota dysbiosis in the third trimester of pregnancy. However, the mechanisms behind these changes remain unknown. Therefore, this study aimed to explore the relationship between the gut microbiome in early pregnancy and PIH occurrence. (2) Methods: A nested case-control study design was used based on the follow-up cohort. Thirty-five PIH patients and thirty-five matched healthy pregnant women were selected as controls. The gut microbiome profiles were assessed in the first trimester using metagenomic sequencing. (3) Results: Diversity analyses showed that microbiota diversity was altered in early pregnancy. At the species level, eight bacterial species were enriched in healthy controls: , , , , , , and . Conversely, , and were enriched in PIH patients. The results of functional analysis showed that the changes in these different microorganisms may affect the blood pressure of pregnant women by affecting the metabolism of vitamin K, sphingolipid, lipid acid and glycine. (4) Conclusion: Microbiota dysbiosis in PIH patients begins in the first trimester of pregnancy, and this may be associated with the occurrence of PIH. Bacterial pathway analyses suggest that the gut microbiome might lead to the development of PIH through the alterations of function modules.
Topics: Humans; Female; Pregnancy; Gastrointestinal Microbiome; Dysbiosis; Case-Control Studies; Hypertension, Pregnancy-Induced; Blood Pressure; Bacteria
PubMed: 36364844
DOI: 10.3390/nu14214582 -
Microbiome Jul 2023Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant...
BACKGROUND
Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (V ), the within-individual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced V could effectively shift gut microbiome composition; reshape the inflammatory response, triglyceride, and cholesterol levels; and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the V of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n = 36) and high (n = 34) V of LS. Partial least square-discriminant analysis and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations.
RESULTS
We identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the V rabbit populations of over than 80%. Compared to the high V population, the low V (resilient) population was characterized by an underrepresentation of Megasphaera sp., Acetatifactor muris, Bacteroidetes rodentium, Ruminococcus bromii, Bacteroidetes togonis, and Eggerthella sp. and greater abundances of Alistipes shahii, Alistipes putredinis, Odoribacter splanchnicus, Limosilactobacillus fermentum, and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience.
CONCLUSIONS
This is the first study to show that selection for V of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the V rabbit populations. Video Abstract.
Topics: Animals; Rabbits; Gastrointestinal Microbiome; Feces; Microbiota; Phenotype; Metagenome
PubMed: 37400907
DOI: 10.1186/s40168-023-01580-4 -
Liver International : Official Journal... May 2024Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and...
BACKGROUND AND AIMS
Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients.
METHODS
113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4.
RESULTS
We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV.
CONCLUSIONS
In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Escherichia coli; Liver; Fibrosis; Bariatric Surgery; Metabolome; Glycerophospholipids; Glucose; Obesity, Morbid
PubMed: 38353022
DOI: 10.1111/liv.15864 -
European Journal of Immunology May 2024HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist,...
HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist, vesatolimod, was previously associated with a modest delay in viral rebound following analytical treatment interruption in HIV controllers (HCs). Using a retrospective analysis of fecal samples from HCs treated with vesatolimod or placebo (NCT03060447), people with chronic HIV (CH; NCT02858401) or without HIV (PWOH), we examined fecal microbiome profile in HCs before/after treatment, and in CH and PWOH. Microbiome diversity and abundance were compared between groups to investigate the association between specific phyla/species, immune biomarkers, and viral outcomes during treatment interruption. Although there were no significant differences in gut microbiome diversity between people with and without HIV, HCs, and CH shared common features that distinguished them from PWOH. there was a trend toward greater microbiome diversity among HCs. Treatment with vesatolimod reduced dysbiosis in HCs. Firmicutes positively correlated with T-cell activation, while Bacteroidetes and Euryarchaeota inversely correlated with TLR7-mediated immune activation. Specific types of fecal microbiome abundance (e.g. Alistipes putredinis) positively correlated with HIV rebound. In conclusion, variability in the composition of the fecal microbiome is associated with markers of immune activation following vesatolimod treatment and ART interruption.
PubMed: 38727191
DOI: 10.1002/eji.202350809 -
Frontiers in Cellular and Infection... 2022It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is...
It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of "harmful bacteria" such as , , unclassified, , and and decreased levels of "beneficial bacteria" such as , , , , , and . Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.
Topics: Adult; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Male; Metabolic Syndrome; Polyamines; gamma-Glutamyltransferase
PubMed: 35967853
DOI: 10.3389/fcimb.2022.946757 -
The ISME Journal May 2021Candida albicans is a leading cause of life-threatening hospital-acquired infections and can lead to Candidemia with sepsis-like symptoms and high mortality rates. We...
Candida albicans is a leading cause of life-threatening hospital-acquired infections and can lead to Candidemia with sepsis-like symptoms and high mortality rates. We reconstructed a genome-scale C. albicans metabolic model to investigate bacterial-fungal metabolic interactions in the gut as determinants of fungal abundance. We optimized the predictive capacity of our model using wild type and mutant C. albicans growth data and used it for in silico metabolic interaction predictions. Our analysis of more than 900 paired fungal-bacterial metabolic models predicted key gut bacterial species modulating C. albicans colonization levels. Among the studied microbes, Alistipes putredinis was predicted to negatively affect C. albicans levels. We confirmed these findings by metagenomic sequencing of stool samples from 24 human subjects and by fungal growth experiments in bacterial spent media. Furthermore, our pairwise simulations guided us to specific metabolites with promoting or inhibitory effect to the fungus when exposed in defined media under carbon and nitrogen limitation. Our study demonstrates that in silico metabolic prediction can lead to the identification of gut microbiome features that can significantly affect potentially harmful levels of C. albicans.
Topics: Bacteria; Bacteroidetes; Candida albicans; Gastrointestinal Microbiome; Humans; Metagenomics
PubMed: 33323978
DOI: 10.1038/s41396-020-00848-z