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Nutrients Aug 2022In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a...
In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% / luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of , , , , and species increased in the LCD group compared to the other two groups, whereas the abundance of , family, , and the genus increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.
Topics: Amino Acids; Animals; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Gastrointestinal Microbiome; Male; Mice; Obesity; Sarcopenia; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Sorbitol
PubMed: 36079789
DOI: 10.3390/nu14173531 -
MSystems Apr 2023Human gut dysbiosis is associated with type 2 diabetes mellitus (T2DM); however, the gut microbiome in pregnant women with pregestational type 2 diabetes mellitus (PGDM)...
Human gut dysbiosis is associated with type 2 diabetes mellitus (T2DM); however, the gut microbiome in pregnant women with pregestational type 2 diabetes mellitus (PGDM) remains unexplored. We investigated the alterations in the gut microbiota composition in pregnant women with or without PGDM. The gut microbiota was examined using 16S rRNA sequencing data of 234 maternal fecal samples that were collected during the first (T1), second (T2), and third (T3) trimesters. The PGDM group presented a reduction in the number of gut bacteria taxonomies as the pregnancies progressed. Linear discriminant analyses revealed that , , and Roseburia intestinalis were enriched in the PGDM group, whereas Bacteroides vulgatus, Faecalibacterium prausnitzii, Eubacterium rectale, Bacteroides uniformis, Eubacterium eligens, , Bacteroides fragilis, , , R-7, Roseburia inulinivorans, Streptococcus oralis, Prevotella melaninogenica, Neisseria perflava, Bacteroides ovatus, Bacteroides caccae, Veillonella dispar, and Haemophilus parainfluenzae were overrepresented in the control group. Correlation analyses showed that the PGDM-enriched taxa were correlated with higher blood glucose levels during pregnancy, whereas the taxonomic biomarkers of normoglycemic pregnancies exhibited negative correlations with glycemic traits. The microbial networks in the PGDM group comprised weaker microbial interactions than those in the control group. Our study reveals the distinct characteristics of the gut microbiota composition based on gestational ages between normoglycemic and PGDM pregnancies. Further longitudinal research involving women with T2DM at preconception stages and investigations using shotgun metagenomic sequencing should be performed to elucidate the relationships between specific bacterial functions and PGDM metabolic statuses during pregnancy and to identify potential therapeutic targets. The incidence of pregestational type 2 diabetes mellitus (PGDM) is increasing, with high rates of serious adverse maternal and neonatal outcomes that are strongly correlated with hyperglycemia. Recent studies have shown that type 2 diabetes mellitus is associated with gut microbial dysbiosis; however, the gut microbiome composition and its associations with the metabolic features of patients with PGDM remain largely unknown. In this study, we investigated the changes in the gut microbiota composition in pregnant women with and without PGDM. We identified differential taxa that may be correlated with maternal metabolic statuses during pregnancy. Additionally, we observed that the number of taxonomic and microbial networks of gut bacteria were distinctly reduced in women with hyperglycemia as their pregnancies progressed. These results extend our understanding of the associations between the gut microbial composition, PGDM-related metabolic changes, and pregnancy outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Pregnant Women; Dysbiosis; RNA, Ribosomal, 16S; Pregnancy Outcome; Hyperglycemia
PubMed: 36853013
DOI: 10.1128/msystems.01146-22 -
MSystems Apr 2024The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein...
The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that possesses a set of 156 proteases with putative intracellular and extracellular localization and allowed to identify amino acid transporters and metabolic pathways. We developed a fully curated genome-scale metabolic model of that incorporated its proteolytic activity and simulated its growth and production of fermentation-related metabolites in response to the different growth media. We validated the model by comparing the predicted phenotype to experimental data. The model accurately predicted 's growth and metabolite production ( = 0.92 for the training set and = 0.89 for the validation set). We found that accounting for both ATP consumption related to proteolysis, and whey protein accessibility is necessary for accurate predictions of metabolites production. These results provide insights into 's adaptation to a high-protein diet and its ability to utilize proteins as a source of nutrition. The proposed model provides a useful tool for understanding the feeding mechanism of in the gut microbiome.IMPORTANCEMicrobial proteolysis is understudied despite the availability of dietary proteins for the gut microbiota. Here, the proteolytic potential of the gut symbiont was analyzed for the first time using pan-genomics. This sketches a well-equipped bacteria for protein breakdown, capable of producing 156 different proteases with a broad spectrum of cleavage targets. This functional potential was confirmed by the enhancement of growth and metabolic activities at high protein levels. Proteolysis was included in a metabolic model which was fitted with the experiments and validated on external data. This model pinpoints the links between protein availability and short-chain fatty acids production, and the importance for to gain access to glutamate and asparagine to promote growth. This integrated approach can be generalized to other symbionts and upscaled to complex microbiota to get insights into the ecological impact of proteins on the gut microbiota.
Topics: Humans; Proteolysis; Bacteria; Fatty Acids, Volatile; Peptide Hydrolases; Bacteroides
PubMed: 38517169
DOI: 10.1128/msystems.00153-24 -
The Journal of International Medical... Oct 2021is an anaerobic bacterium with a reportedly high isolation rate; however, it rarely causes bloodstream infections. Patients with hypertension are at increased risk of...
is an anaerobic bacterium with a reportedly high isolation rate; however, it rarely causes bloodstream infections. Patients with hypertension are at increased risk of developing anaerobic bacterial infection. In this study, we report a case of bacteremia caused by in a patient with renal hypertension and gastrointestinal hemorrhage. This study describes the clinical manifestations of bloodstream infection involving to provide guidance for laboratory technicians and clinicians. A 42-year-old Chinese man was admitted for gastrointestinal hemorrhage and subsequently diagnosed with anaerobic blood infection. The pathogenic bacteria isolated from anaerobic blood culture bottles were identified as by using an automatic bacterial identification instrument and mass spectrometry (MS). is an intestinal opportunistic pathogen that can invade the intestinal mucosa and cause anaerobic bloodstream infection. Two or more sets of blood cultures and MS identification can greatly improve the positive detection rate of blood cultures of anaerobic bacteria. Furthermore, the increased drug resistance of anaerobic bacteria necessitates drug sensitivity tests for anaerobic bacteria in many hospitals. Thus, the early prevention and control of primary diseases with appropriate diagnoses and timely anti-infection therapies are necessary to reduce bloodstream infection.
Topics: Adult; Bacteroides; Base Composition; Humans; Hypertension, Renal; Male; Phylogeny; RNA, Ribosomal, 16S; Sepsis; Sequence Analysis, DNA
PubMed: 34704482
DOI: 10.1177/03000605211047277 -
Microbiome Dec 2021Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to...
BACKGROUND
Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984-1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]).
RESULTS
We found that family Succinivibrionaceae, S24-7, Mogibacteriaceae, Coriobacteriaceae, and Erysipelotrichaceae were significantly higher (p<0.05), whereas Odoribacteraceae, Verucomicrobiaceae, Bacteroidaceae, Barnesiellaceae, and Rikenellaceae were significantly lower (p<0.05), in SC before HIV-1 infection compared to NC. At the species level, Prevotella stercorea, Eubacterium biforme, and Collinsella aerofaciens were significantly higher (p<0.05), and Eubacterium dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques, Bacteroides fragilis, Bacteroides caccae, Alistipes putredinis, Akkermansia muciniphila, Bacteroides uniformis, and Bacteroides ovatus were significantly lower (p<0.05) in SC before HIV-1 infection compared to NC. After HIV-1 infection, family Prevotellaceae and Victivallaceae and species Bacteroides fragilis and Eubacterium cylindroides were significantly higher (p<0.05) in SC who developed AIDS within 5 years compared to the SC who were AIDS free for more than 10 years without antiretroviral therapy (ART). In addition, family Victivallaceae and species Prevotella stercorea, Coprococcus eutactus, and Butyrivibrio crossotus were significantly higher (p<0.05) and Gemmiger formicilis and Blautia obeum were significantly lower (p<0.05) after HIV-1 infection in SC who developed AIDS within 5-10 years compared to the SC who were AIDS-free for more than 10 years without ART. Furthermore, plasma inflammatory cytokine levels of sCD14, sCD163, interleukin 6, and lipopolysaccharide binding protein were significantly higher in SC with p<0.05 before HIV-1 infection compared to NC.
CONCLUSIONS
Our results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. Video abstract.
Topics: Cohort Studies; Female; Gastrointestinal Microbiome; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Sexual and Gender Minorities
PubMed: 34879869
DOI: 10.1186/s40168-021-01168-w -
Journal of Clinical Gastroenterology Aug 2014Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein...
BACKGROUND AND GOALS
Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy.
MATERIALS AND METHODS
Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet.
RESULTS
Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet.
CONCLUSIONS
Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.
Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Antibodies, Fungal; Bacterial Outer Membrane Proteins; Biomarkers; Celiac Disease; Diet, Gluten-Free; Female; GTP-Binding Proteins; Humans; Immunoglobulin A; Immunoglobulin G; Male; Middle Aged; Protein Glutamine gamma Glutamyltransferase 2; Saccharomyces cerevisiae Proteins; Superantigens; Transglutaminases; Young Adult
PubMed: 24518796
DOI: 10.1097/MCG.0000000000000089 -
Applied and Environmental Microbiology Jun 2020Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Previous studies have shown that , the major phylum of gut microbiota...
Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Previous studies have shown that , the major phylum of gut microbiota together with , impact IgA production. However, the relative abundances of species of responsible for IgA production were not well understood. In the present study, we identified some specific species that were associated with gut IgA induction by -based profiling of species distribution among The levels of IgA and the expression of the gene encoding activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were increased in soluble high-fiber diet (sHFD)-fed mice. We found that was the most abundant species in both sHFD- and normal diet-fed mice. In addition, the gut IgA levels were associated with the relative abundance of group species such as , , and Conversely, the ratio of to other species was reduced in insoluble high-fiber diet fed- and no-fiber diet-fed mice. To investigate whether increases IgA production, we generated monoassociated mice and found increased gut IgA production and AID expression. Collectively, soluble dietary fiber increases the ratio of gut group, such as , and IgA production. This might improve gut immune function, thereby protecting against bowel pathogens and reducing the incidence of inflammatory bowel diseases. Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Gut microbiota impact IgA production, but the specific species responsible for IgA production remain largely elusive. Previous studies have shown that IgA and , the major phyla of gut microbiota, were increased in soluble high-fiber diet-fed mice. We show here that the levels of IgA in the gut and the expression of activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were correlated with the abundance of group species such as , , and monoassociated mice increased gut IgA production and AID expression. Soluble dietary fiber may improve gut immune function, thereby protecting against bowel pathogens and reducing inflammatory bowel diseases.
Topics: Animals; Bacteroides fragilis; Chaperonin 60; Dietary Fiber; Female; Gene Expression Profiling; Immunoglobulin A; Mice; Mice, Inbred C57BL; Mitochondrial Proteins
PubMed: 32332136
DOI: 10.1128/AEM.00405-20 -
Frontiers in Bioengineering and... 2020Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled cultivation and up-to-date...
Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled cultivation and up-to-date analytical methods make possible the systematic evaluation of the underlying mechanisms of complex interactions between the members of microbial consortia. Information on reproducing fecal microbial consortia can be used for various clinical and biotechnological applications. In this study, chemostat and changestat cultures were used to elucidate the effects of the physiologically relevant range of dilution rates on the growth and metabolism of adult fecal microbiota. The dilution rate was kept either at = 0.05 or = 0.2 1/h in chemostat cultures, while gradually changing from 0.05 to 0.2 1/h in the A-stat and from 0.2 to 0.05 1/h in the De-stat. Apple pectin as a substrate was used in the chemostat experiments and apple pectin or birch xylan in the changestat experiments, in the presence of porcine mucin in all cases. The analyses were comprised of HPLC for organic acids, UPLC for amino acids, GC for gas composition, 16S-rDNA sequencing for microbial composition, and growth parameter calculations. It was shown that the abundance of most bacterial taxa was determined by the dilution rate on both substrates. , , and were prevalent within the whole range of dilution rates. and Ruminococcaceae UCG-013 were significantly enriched at = 0.05 1/h, while , Lachnospiraceae unclassified and clearly preferred = 0.2 1/h. In the chemostat cultures, the production of organic acids and gases from pectin was related to the dilution rate. The ratio of acetate, propionate and butyrate was 5:2:1 ( = 0.05 1/h) and 14:2:1 ( = 0.2 1/h). It was shown that the growth rate-related characteristics of the fecal microbiota were concise in both directions between = 0.05 and 0.2 1/h. Reproducible adaptation of the fecal microbiota was shown in the continuous culture with a changing dilution rate: changestat. Consortia cultivation is a promising approach for research purposes and several biotechnological applications, including the production of multi-strain probiotics and fecal transplantation mixtures.
PubMed: 32117913
DOI: 10.3389/fbioe.2020.00024 -
Nutrients Apr 2020Risk of celiac disease (CD) is increased in relatives of CD patients due to genetic and possible environmental factors. We recently reported increased seropositivity to...
Risk of celiac disease (CD) is increased in relatives of CD patients due to genetic and possible environmental factors. We recently reported increased seropositivity to anti- (ASCA), -associated sequence (anti-I2) and TonB-linked outer membrane protein (anti-OmpW) antibodies in CD. We hypothesized these markers also to be overrepresented in relatives. Seropositivity and levels of ASCA, anti-I2 and anti-OmpW were compared between 463 first-degree relatives, 58 untreated and 55 treated CD patients, and 80 controls. CD-associated human leukocyte antigen (HLA)-haplotypes and transglutaminase (tTGab) and endomysium (EmA) antibodies were determined. One or more of the microbial antibodies was present in 75% of relatives, 97% of untreated and 87% of treated CD patients and 44% of the controls. The relatives had higher median ASCA IgA (9.13 vs. 4.50 U/mL, < 0.001), ASCA IgG (8.91 vs. 5.75 U/mL, < 0.001) and anti-I2 (absorbance 0.74 vs. 0.32, < 0.001) levels than controls. There was a weak, positive correlation between tTGab and ASCA (r = 0.31, < 0.001). Seropositivity was not significantly associated with HLA. To conclude, seropositivity to microbial markers was more common and ASCA and anti-I2 levels higher in relatives of CD patients than controls. These findings were not associated with HLA, suggesting the role of other genetic and environmental factors.
Topics: Adult; Antibodies, Bacterial; Antibodies, Fungal; Celiac Disease; Family; Female; HLA Antigens; Humans; Immunoglobulin A; Male; Middle Aged; Pseudomonas fluorescens; Saccharomyces cerevisiae; Transglutaminases
PubMed: 32294897
DOI: 10.3390/nu12041073 -
Hepatology (Baltimore, Md.) Apr 2022Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population...
BACKGROUND AND AIMS
Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population at high risk for liver fibrosis, are urgently needed. We aimed to characterize the gut microbiome signatures and related biological functions associated with liver fibrosis in Hispanics and identify environmental and genetic factors affecting them.
APPROACH AND RESULTS
Subjects of the population-based Cameron County Hispanic Cohort (CCHC; n = 217) were screened by vibration-controlled transient elastography (FibroScan). Among them, 144 (66.7%) had steatosis and 28 (13.0%) had liver fibrosis. The gut microbiome of subjects with liver fibrosis was enriched with immunogenic commensals (e.g., Prevotella copri, Holdemanella, Clostridiaceae 1) and depleted of Bacteroides caccae, Parabacteroides distasonis, Enterobacter, and Marinifilaceae. The liver fibrosis-associated metagenome was characterized by changes in the urea cycle, L-citrulline biosynthesis and creatinine degradation pathways, and altered synthesis of B vitamins and lipoic acid. These metagenomic changes strongly correlated with the depletion of Parabacteroides distasonis and enrichment of Prevotella and Holdemanella. Liver fibrosis was also associated with depletion of bacterial pathways related to L-fucose biosynthesis. Alcohol consumption, even moderate, was associated with high Prevotella abundance. The single-nucleotide polymorphisms rs3769502 and rs7573751 in the NCK adaptor protein 2 (NCK2) gene positively associated with high Prevotella abundance.
CONCLUSION
Hispanics with liver fibrosis display microbiome profiles and associated functional changes that may promote oxidative stress and a proinflammatory environment. These microbiome signatures, together with NCK2 polymorphisms, may have utility in risk modeling and disease prevention in this high-risk population.
Topics: Bacteroidetes; Carcinoma, Hepatocellular; Gastrointestinal Microbiome; Hispanic or Latino; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 34633706
DOI: 10.1002/hep.32197