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Microbiology Spectrum Dec 2022Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC...
Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of sp. N15.MGS-57. The higher richness of sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.
Topics: Female; Humans; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Obesity; Endometrial Neoplasms; Feces; Biomarkers; Fatty Acids; Indole Alkaloids; TOR Serine-Threonine Kinases; Tumor Microenvironment
PubMed: 36227107
DOI: 10.1128/spectrum.02612-22 -
PloS One 2020Alteration of gut microbiome composition has been linked to cardiovascular diseases. To identify specific bacterial communities associated with coronary artery diseases...
Alteration of gut microbiome composition has been linked to cardiovascular diseases. To identify specific bacterial communities associated with coronary artery diseases (CAD), we conducted a case-control study with 53 advanced CAD patients and 53 age-, sex-, race-, and BMI-matched controls. V3-V5 regions of the 16S rDNA from the fecal gut material were analyzed to compare the gut microbiome composition between CAD patients and controls. The alpha diversity, including Chao-1, Shannon-index, and the number of observed taxonomy units were significantly decreased in CAD patients indicating, decreased richness and evenness of gut microbiome. Among 23 different abundant taxa at the genus level, 12 taxa belonged to Lachnospiraceae family, which are known to produce butyrate. Further, we identified five taxa which showed more than two log-fold changes with maximum proportion >0.002, including Ruminococcus gnavus, Lachnospiraceae anaerosporobacter, Lachnospiraceae NK4B4 group, Lachnospiraceae UCG-004, and Ruminococcus gauvreauii. After adjustment for coronary risk factors (diabetes mellitus and dyslipidemia), decreased relative abundance of Lachnospiraceae NK4B4 group and Ruminococcus Gauvreauii and increased relative abundance of Ruminococcus gnavus were associated with the presence of advanced CAD. The observed differences in taxa between CAD patients and controls in this study may provide insight into the link between the gut microbiome and CAD.
Topics: Aged; Base Sequence; Case-Control Studies; Clostridiales; Coronary Artery Disease; Feces; Female; Gastrointestinal Microbiome; Humans; Logistic Models; Male; Middle Aged; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 31995569
DOI: 10.1371/journal.pone.0227147 -
MBio Mar 2021, , and are the three predominant cellulolytic bacterial species found in the rumen. studies have shown that these species compete for adherence to, and growth upon,...
, , and are the three predominant cellulolytic bacterial species found in the rumen. studies have shown that these species compete for adherence to, and growth upon, cellulosic biomass. Yet their molecular interactions have not heretofore been examined. Gnotobiotically raised lambs harboring a 17-h-old immature microbiota devoid of culturable cellulolytic bacteria and methanogens were inoculated first with S85 and sp. strain 87.7, and 5 months later, the lambs were inoculated with 8 and FD-1. Longitudinal samples were collected and profiled for population dynamics, gene expression, fibrolytic enzyme activity, fibrolysis, and metabolite profiling. Quantitative PCR, metagenome and metatranscriptome data show that establishes at high levels initially but is gradually outcompeted following the introduction of the ruminococci. This shift resulted in an increase in carboxymethyl cellulase (CMCase) and xylanase activities but not in greater fibrolysis, suggesting that and ruminococci deploy different but equally effective means to degrade plant cell walls. Expression profiles showed that relied upon outer membrane vesicles and a diverse repertoire of CAZymes, while and preferred type IV pili and either CBM37-harboring or cellulosomal carbohydrate-active enzymes (CAZymes), respectively. The changes in cellulolytics also affected the rumen metabolome, including an increase in acetate and butyrate at the expense of propionate. In conclusion, this study provides the first demonstration of competition between the three predominant cellulolytic bacteria and provides insight on the influence of these ecological interactions on rumen fibrolytic function and metabolomic response. Ruminant animals, including cattle and sheep, depend on their rumen microbiota to digest plant biomass and convert it into absorbable energy. Considering that the extent of meat and milk production depends on the efficiency of the microbiota to deconstruct plant cell walls, the functionality of predominant rumen cellulolytic bacteria, , , and , has been extensively studied to obtain a better knowledge of how they operate to hydrolyze polysaccharides and ultimately find ways to enhance animal production. This study provides the first evidence of competitions between and the two species. It shows that a simple disequilibrium within the cellulolytic community has repercussions on the rumen metabolome and fermentation end products. This finding will have to be considered in the future when determining strategies aiming at directing rumen fermentations for animal production.
Topics: Age Factors; Animals; Female; Fibrobacter; Gene Expression Profiling; Germ-Free Life; Male; Metagenome; Metagenomics; Microbial Interactions; RNA, Ribosomal, 16S; Rumen; Ruminococcus; Sheep
PubMed: 33658330
DOI: 10.1128/mBio.03533-20 -
Food & Nutrition Research 2021Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the...
BACKGROUND
Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the metabolic and inflammatory responses of the mother. However, investigations on GM in PE are rare.
OBJECTIVE
The objective of the present study was to investigate the changes of GM in PE and how to alter the GM composition in PE by dietary or dietary supplements.
DESIGN
We analyzed the composition changes in GM as well as the relationship between bacteria of different genera and clinical indices by amplifying the V4 region of the 16S ribosomal RNA gene in 12 PE patients and eight healthy pregnant women in East China.
RESULTS
In the PE group, the Observed Species Index was lower than that in the control group, indicating that the α-diversity of the microbiome in the PE group decreased. At phylum, family, and genus levels, the relative abundance of different bacteria in PE patients displayed substantial differences to those from healthy women. We noted a decreased abundance of bacteria of the phylum Actinobacteria ( = 0.042), decreased abundance of bacteria of the family Bifidobacteriaceae ( = 0.039), increased abundance of bacteria of the genus ( = 0.026) and ( = 0.048), and decreased abundance of bacteria of the genus ( = 0.038) Among three enriched genera, bacteria of the genus showed a negative correlation with the systolic blood pressure (SBP), diastolic blood pressure (DBP), and dyslipidemia, which involved glucose metabolism, lipid metabolism, and the oxidative-phosphorylation pathway. The increased abundance of bacteria of the genera and was positively correlated with obesity and dyslipidemia, which involved lipid metabolism, glycosyltransferases, biotin metabolism, and the oxidative-phosphorylation pathways. Moreover, women in the PE group ate more than women in the control group, so fetuses were more prone to overnutrition in the PE group.
CONCLUSION
There is a potential for GM dysbiosis in PE patients, and they could be prone to suffer from metabolic syndrome. We speculate that alterations in the abundance of bacteria of certain genera (e.g. increased abundance of and , and decreased abundance of ) were associated with PE development to some degree. Our data could help to monitor the health of pregnant women and may be helpful for preventing and assisting treatment of PE by increasing dietary fiber or probiotics supplement.
PubMed: 34262418
DOI: 10.29219/fnr.v65.5781 -
Frontiers in Microbiology 2018Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the...
Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader ATCC 29149, and L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of and grown on mucin or starch as sole carbon source, we showed that starch degradation by supported the growth of whereas did not benefit from mucin degradation by . Further we analyzed the growth (quantitative PCR), metabolite production (H NMR analysis), and bacterial transcriptional response (RNA-Seq) of cultured with RS or soluble starch (SS) in the presence or absence of . In co-culture fermentations on starch, H NMR analysis showed that benefits from transient glucose and malto-oligosaccharides released by upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of induced changes in transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of to utilize starch degradation products. In the RS co-culture, showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of . Together this study showed a direct competition between and on RS, suggesting that , the population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
PubMed: 30455672
DOI: 10.3389/fmicb.2018.02558 -
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 -
Journal of Dairy Science Oct 2022Diet starch and fiber contents influence the rumen microbial profile and its fermentation products, yet no information exists about the effects of these dietary...
Diet starch and fiber contents influence the rumen microbial profile and its fermentation products, yet no information exists about the effects of these dietary carbohydrate fractions on the metabolic activity of these microbes. The objective of this experiment was to evaluate the effects of dietary carbohydrate profile changes on the rumen meta-proteome profile. Eight cannulated Holstein cows were assigned to the study as part of a 4 × 4 Latin square design with a 2 × 2 factorial treatment arrangement including four 28-d periods. Cows received 1 of 4 dietary treatments on a dry matter (DM) basis. Diets included different concentrations of rumen fermentable starch (RFS) and physically effective undigested NDF (peuNDF240) content in the diet: (1) low peuNDF240, low RFS (LNLS); (2) high peuNDF240, low RFS (HNLS); (3) low peuNDF240, high RFS (LNHS); and (4) high peuNDF240, high RFS (HNHS). Rumen fluid samples were collected from each cow on the last 2 d of each period at 3 time points (0600, 1000, and 1400 h). The microbial protein fraction was isolated, isobarically labeled, and analyzed using liquid chromatography combined with tandem mass spectrometry techniques. Product ion spectra were searched using the SEQUEST search on Proteome Discoverer 2.4 (Thermo Scientific) against 71 curated microbe-specific databases. Data were analyzed using PROC MIXED procedure in SAS 9.4 (SAS Institute Inc.). A total of 138 proteins were characterized across 26 of the searched microbial species. In total, 46 proteins were affected by treatments across 17 of the searched microbial species. Of these 46 proteins, 28 were affected by RFS content across 13 microbial species, with 20 proteins having higher abundance with higher dietary RFS and 8 proteins having higher abundance with lower dietary RFS. The majority of these proteins have roles in energetics, carbon metabolism, and protein synthesis. Examples include pyruvate, phosphate dikinase (Ruminococcus albus SY3), 30S ribosomal protein S11 (Clostridium aminophilum), and methyl-coenzyme M reductase subunit α (Methanobrevibacter ruminantium strain 35063), which had higher abundances with higher dietary RFS. Conversely, glutamate dehydrogenase (Butyrivibrio fibrisolvens) and 50S ribosomal protein L5 (Pseudobutyrivibrio ruminis) and L15 (Ruminococcus bromii) had lower abundances with higher dietary RFS content. Among the remaining 18 proteins unaffected by RFS content alone, 5 proteins were affected by peuNDF240 content, and 13 were affected by peuNDF240 × RFS interactions. Our results suggest that the RFS content of the diet may have a greater influence on rumen microbial protein abundances than dietary peuNDF240 content or peuNDF240 × RFS interactions. This research highlights that dietary carbohydrate profile changes can influence rumen microbial protein abundances. Further research is needed to fully characterize the effects of diet on the rumen meta-proteome and manipulate the various roles of rumen microbes. This will aid in designing the strategies to maximize the efficiency of nutrient use in the rumen.
Topics: Animal Feed; Animals; Carbon; Cattle; Diet; Dietary Carbohydrates; Dietary Fiber; Digestion; Female; Fermentation; Glutamate Dehydrogenase; Lactation; Milk; Proteome; Pyruvate, Orthophosphate Dikinase; Rumen; Starch
PubMed: 36028341
DOI: 10.3168/jds.2022-21812 -
PloS One 2022Increasing evidences indicate that gut microbiota composition is associated with multiple inflammatory diseases. However, little is known about how gut microbiota...
Increasing evidences indicate that gut microbiota composition is associated with multiple inflammatory diseases. However, little is known about how gut microbiota changes with age and correlations with gut inflammation at sexual maturity stage of healthy individuals. Elucidating the dynamic changes of gut microbiota in healthy individuals at the sexual maturity stage and correlations with gut inflammation can provide clues for early risk assessment of gut diseases at the sexual maturity stage. Here, the shift in gut bacteria and its relationship with gut inflammation at the sexual maturity stage were explored. Sprague-Dawley rats at the sexual maturity stage were used in this study. 16S rRNA gene sequencing was performed to decipher gut bacteria shifts from the 7th week to the 9th week, and enzyme-linked immunosorbent assay (ELISA) was used to measure gut inflammation and gut barrier permeability. We found an increase in bacterial richness with age and a decrease in bacterial diversity with age. The gut bacteria were primarily dominated by the phyla Firmicutes and Bacteroides and the genus Prevotella. The relative abundance of Firmicutes increased with age, and the relative abundance of Bacteroides decreased with age. There was a positive correlation between body weight and the Firmicutes:Bacteroides ratio. More and more gut microbiota participated in the host gut inflammation and barrier permeability regulation with age. Ruminococcus was the only gut bacteria participated in gut inflammation and barrier permeability regulation both in the 7th week and the 15th week. These results provide a better understanding of the relationship between gut bacteria and gut inflammation in sexually mature rats and show that Ruminococcus may be a potential indicator for early risk assessment of gut inflammation.
Topics: Animals; Bacteria; Bacteroides; Firmicutes; Gastrointestinal Microbiome; Inflammation; RNA, Ribosomal, 16S; Rats; Rats, Sprague-Dawley; Ruminococcus
PubMed: 35290412
DOI: 10.1371/journal.pone.0265430 -
Indian Journal of Endocrinology and... 2023Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM).
BACKGROUND
Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM).
OBJECTIVES
To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control.
METHODOLOGY
Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis.
RESULTS
The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria and showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels ( < 0.05). and were important negative predictors of glycaemic control ( < 0.05).
CONCLUSION
Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like and (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.
PubMed: 38107732
DOI: 10.4103/ijem.ijem_22_22 -
International Journal of Molecular... Jan 2021The gut microbiota has emerged as a key factor in the pathogenesis of intestinal viruses, including enteroviruses, noroviruses and rotaviruses (RVs), where stimulatory...
The gut microbiota has emerged as a key factor in the pathogenesis of intestinal viruses, including enteroviruses, noroviruses and rotaviruses (RVs), where stimulatory and inhibitory effects on infectivity have been reported. With the aim of determining whether members of the microbiota interact with RVs during infection, a combination of anti-RV antibody labeling, fluorescence-activated cell sorting and 16S rRNA amplicon sequencing was used to characterize the interaction between specific bacteria and RV in stool samples of children suffering from diarrhea produced by G1P[8] RV. The genera and were identified as RV binders in stools, displaying enrichments between 4.8- and 5.4-fold compared to samples nonlabeled with anti-RV antibodies. In vitro binding of the G1P[8] Wa human RV strain to two human isolates was confirmed by fluorescence microscopy. Analysis in with antibodies directed to several histo-blood group antigens (HBGAs) indicated that these bacteria express HBGA-like substances on their surfaces, which can be the target for RV binding. Furthermore, in vitro infection of the Wa strain in differentiated Caco-2 cells was significantly reduced by incubation with These data, together with previous findings showing a negative correlation between levels and antibody titers to RV in healthy individuals, suggest a pivotal interaction between this bacterial group and human RV. These results reveal likely mechanisms of how specific bacterial taxa of the intestinal microbiota could negatively affect RV infection and open new possibilities for antiviral strategies.
Topics: Bacterial Proteins; Caco-2 Cells; Child, Preschool; Gastrointestinal Microbiome; Humans; Intestines; Protein Binding; Rotavirus; Rotavirus Infections; Ruminococcus
PubMed: 33498321
DOI: 10.3390/ijms22031010