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Biology of Blood and Marrow... Apr 2020Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used...
Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used prophylactic antibacterial antibiotic during intensive chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT), on the gut microbiota in 2 cohorts of patients, 1 cohort comprising 20 patients with acute leukemia receiving intensive chemotherapy and the other cohort comprising 20 allo-HCT recipients. 16S rRNA gene sequencing of thrice-weekly collected stool samples permitted a comparison between intervals with no antibacterial antibiotic exposure and those with only LEVO exposure. In mixed-effects modeling, the only variables influenced by LEVO were the relative abundances of Parabacteroides (regression coefficient, -.063; 99% confidence interval [CI], -.102 to -.024) and Blautia (regression coefficient, .050; 99% CI, .004 to .095). Other taxa and microbiota diversity were unaffected. Overall, the effect of LEVO on the gut microbiota in these cohorts was mild.
Topics: Dysbiosis; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Humans; Levofloxacin; RNA, Ribosomal, 16S
PubMed: 31870930
DOI: 10.1016/j.bbmt.2019.12.722 -
Obesity Surgery Jul 2022Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota...
PURPOSE
Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota after sleeve gastrectomy (SG) and SG plus truncal vagotomy (SG-TV) and identify specific microbes that may contribute to the improvement of obesity after surgeries.
MATERIALS AND METHODS
Forty high-fat diet-induced obesity (DIO) mice were randomized to SG, SG-TV, or sham operation (SH) groups. Body weight (BW) and fast blood glucose (FBG) were measured before and 1, 2, 4, 8, and 12 weeks post-operatively. Fecal samples were collected before and at post-operative week 12 and profiled using 16S rRNA relative and absolute quantitative sequencing.
RESULTS
After the surgery, the SG and SG-TV surgeries significantly reduce BW and FBG levels compared with SH, and the SG-TV achieved better effects than SG. A decreasing trend in alpha diversity of gut microbiota and significant changes in taxonomic composition were observed after surgeries. Then, we identified a set of microbes and pathways significantly different in abundance after BS. The genus Parabacteroides and one pathway (polyketide sugar unit biosynthesis) increased in SG-TV group specially, which was also negatively correlated with BW and FBG.
CONCLUSION
SG and SG-TV indeed achieve effects of weight loss, but TV could enhance the efficacy of SG. The identified different microbes and pathways, like Parabacteroides, polyketide sugar unit biosynthesis, may partly mediate the beneficial effects of BS, and thus possibly contribute to the development of novel bacteria-based therapeutic approaches.
Topics: Animals; Bariatric Surgery; Gastrectomy; Mice; Obesity; Obesity, Morbid; Polyketides; RNA, Ribosomal, 16S; Sugars; Vagotomy, Truncal; Weight Loss
PubMed: 35546385
DOI: 10.1007/s11695-022-06017-9 -
Journal of Applied Microbiology Jul 2011To develop species-specific monitoring techniques for rapid detection of Bacteroides and Parabacteroides inhabiting the mouse intestine by fluorescence in situ...
Design of species-specific oligonucleotide probes for the detection of Bacteroides and Parabacteroides by fluorescence in situ hybridization and their application to the analysis of mouse caecal Bacteroides-Parabacteroides microbiota.
AIMS
To develop species-specific monitoring techniques for rapid detection of Bacteroides and Parabacteroides inhabiting the mouse intestine by fluorescence in situ hybridization.
METHODS AND RESULTS
The specificity of oligonucleotide probes was evaluated by fluorescence whole-cell hybridization. Oligonucleotide probes specific for each species hybridized only with the target bacteria. Using these probes, caecal Bacteroides-Parabacteroides microbiota of conventional mice and specific pathogen-free (SPF) mice from three different breeders were analysed. It was shown that Bacteroides acidifaciens Group-1, Group-2 and Group-3 were dominant in conventional mice and SPF mice from two out of three breeders. Bacteroides vulgatus and Parabacteroides distasonis were detected in one of these two SPF breeding colonies in addition to Bact. acidifaciens. SPF mice of the remaining breeder harboured characteristic Bacteroides-Parabacteroides microbiota, consisting of Bacteroides sp. ASF519 and Bacteroides caccae.
CONCLUSIONS
Bacteroides acidifaciens is the dominant and most typical species in the mouse Bacteroides-Parabacteroides microbiota. The Group-3 was identified as a novel group and revealed to occupy a major niche together with Bact. acidifaciens Group-1 and Group-2.
SIGNIFICANCE AND IMPACT OF THE STUDY
The species-specific probe set developed in this study was the efficient tool for rapid detection of target bacterial groups inhabiting the mouse intestine. The results of this study provide important new information on the mouse Bacteroides-Parabacteroides community.
Topics: Animals; Bacteriological Techniques; Bacteroidetes; Cecum; Feces; In Situ Hybridization, Fluorescence; Male; Mice; Mice, Inbred BALB C; Oligonucleotide Probes; RNA, Bacterial; RNA, Ribosomal, 16S; Species Specificity; Specific Pathogen-Free Organisms
PubMed: 21535330
DOI: 10.1111/j.1365-2672.2011.05039.x -
PloS One 2022Premenstrual symptoms can negatively impact the quality of life of women through a range of mood, behavioral, and physical symptoms. The association between the...
PURPOSE
Premenstrual symptoms can negatively impact the quality of life of women through a range of mood, behavioral, and physical symptoms. The association between the microbiota and brain function has been extensively studied. Here, we examined the characteristics of the microbiota in women with premenstrual disorders (PMDs) and the association between premenstrual symptoms and the microbiota.
MATERIALS AND METHODS
In this single center cross-sectional pilot study, we recruited 27 women reporting premenstrual symptoms and 29 women with no serious premenstrual symptoms. Among them, we further selected 21 women experiencing premenstrual symptoms resulting in interference to their social life (PMDs group) and 22 women with no serious premenstrual symptoms and thereby no interference to their social life (control group). The severity of symptoms was evaluated by a premenstrual symptoms questionnaire (PSQ). Inflammatory markers were analyzed in blood samples, including C reactive protein, soluble CD14, and lipopolysaccharide binding protein. Sequencing of 16S ribosomal ribonucleic acid genes was performed on stool samples.
RESULTS
Inflammatory markers in blood samples did not differ significantly between the PMDs and control groups. A difference in beta, but not alpha diversity, was detected for the gut microbiotas of the PMDs and control groups. The relative abundance of the Bacteroidetes phylum was lower in the PMDs group. At the genus level, the prevalence was decreased for Butyricicoccus, Extibacter, Megasphaera, and Parabacteroides and increased for Anaerotaenia in the PMDs group, but after false discovery rate correction, these differences were no longer significant. Linear discriminant effect size analysis revealed a decrease in Extibacter, Butyricicoccus, Megasphaera, and Parabacteroides and an increase in Anaerotaenia in the PMDs group. The PSQ total score correlated with Anaerotaenia, Extibacter, and Parabacteroides. Multiple regression analysis showed that Parabacteroides and Megasphaera negatively predicted the PSQ total score.
CONCLUSION
The properties of the gut microbiota are associated with premenstrual symptoms.
Topics: Bacteroidetes; Clostridiaceae; Clostridiales; Cross-Sectional Studies; Female; Gastrointestinal Microbiome; Humans; Pilot Projects; Premenstrual Syndrome; Quality of Life
PubMed: 35622782
DOI: 10.1371/journal.pone.0268466 -
MBio Aug 2019Studies of the gut microbiota have dramatically increased in recent years as the importance of this microbial ecosystem to human health and disease is better...
Studies of the gut microbiota have dramatically increased in recent years as the importance of this microbial ecosystem to human health and disease is better appreciated. The are the most abundant order of bacteria in the healthy human gut and induce both health-promoting and disease-promoting effects. There are more than 55 species of gut with extensive intraspecies genetic diversity, especially in regions involved in the synthesis of molecules that interact with other bacteria, the host, and the diet. This property necessitates the study of diverse species and strains. In recent years, the genetic toolkit to study these bacteria has greatly expanded, but we still lack a facile system for creating deletion mutants and allelic replacements in diverse strains, especially with the rapid increase in resistance to the two antibiotics used for genetic manipulation. Here, we present a new versatile and highly efficient vector suite that allows the creation of allelic deletions and replacements in multiresistant strains of and using a gain-of-function system based on polysaccharide utilization. These vectors also allow for easy counterselection independent of creating a mutant background strain, using a toxin from a type VI secretion system of Toxin production during counterselection is induced with one of two different molecules, providing flexibility based on strain phenotypes. This family of vectors greatly facilitates functional genetic analyses and extends the range of gut strains that can be genetically modified to include multiresistant strains that are currently genetically intractable with existing genetic tools. We have entered an era when studies of the gut microbiota are transitioning from basic questions of composition and host effects to understanding the microbial molecules that underlie compositional shifts and mediate health and disease processes. The importance of the gut to human health and disease and their potential as a source of engineered live biotherapeutics make these bacteria of particular interest for in-depth mechanistic study. However, there are still barriers to the genetic analysis of diverse strains, limiting our ability to study important host and community phenotypes identified in these strains. Here, we have overcome many of these obstacles by constructing a series of vectors that allow easy genetic manipulation in diverse gut and strains. These constructs fill a critical need and allow streamlined allelic replacement in diverse gut , including the growing number of multiantibiotic-resistant strains present in the modern-day human intestine.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Bacteroides; Bacteroidetes; Drug Resistance, Multiple, Bacterial; Gastrointestinal Microbiome; Genetic Engineering; Genetic Markers; Genetic Vectors; Humans; Inulin; Metalloendopeptidases; Mutation; Promoter Regions, Genetic; Rhamnose
PubMed: 31409684
DOI: 10.1128/mBio.01762-19 -
Microbial Biotechnology Mar 2022Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T , around 37°C). Thyroid hormones are a major regulator for energy...
Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T , around 37°C). Thyroid hormones are a major regulator for energy metabolism and T . The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and T . l-thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and T , whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and T . These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and T in endotherms.
Topics: Animals; Cecum; Gerbillinae; Hyperthyroidism; Thermogenesis; Thyroid Hormones
PubMed: 33729663
DOI: 10.1111/1751-7915.13793 -
Journal of Translational Medicine Jun 2023The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with...
OBJECTIVE
The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC.
METHOD
The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing.
RESULT
The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV.
CONCLUSIONS
The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.
Topics: Humans; Gastrointestinal Microbiome; Interleukin-6; Colorectal Neoplasms; Bacteroidetes; Feces; RNA, Ribosomal, 16S; Tumor Microenvironment
PubMed: 37291572
DOI: 10.1186/s12967-023-04119-1 -
Proceedings of the National Academy of... Aug 2022Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of...
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of autoantibodies and T cells directed at an epitope in the B-chain of insulin (insB:9-23). Analysis of microbial protein sequences with homology to the insB:9-23 sequence revealed 17 peptides showing >50% identity to insB:9-23. Of these 17 peptides, the peptide, found in the normal human gut commensal , activated both human T cell clones from T1D patients and T cell hybridomas from nonobese diabetic (NOD) mice specific to insB:9-23. Immunization of NOD mice with insB:9-23 peptide mimic or insB:9-23 peptide verified immune cross-reactivity. Colonization of female NOD mice with accelerated the development of T1D, increasing macrophages, dendritic cells, and destructive CD8 T cells, while decreasing FoxP3 regulatory T cells. Western blot analysis identified -reacting antibodies in sera of NOD mice colonized with and human T1D patients. Furthermore, adoptive transfer of splenocytes from -treated mice to NOD/SCID mice enhanced disease phenotype in the recipients. Finally, analysis of human children gut microbiome data from a longitudinal DIABIMMUNE study revealed that seroconversion rates (i.e., the proportion of individuals developing two or more autoantibodies) were consistently higher in children whose microbiome harbored sequences capable of producing the peptide compared to individuals who did not harbor it. Taken together, these data demonstrate the potential role of a gut microbiota-derived insB:9-23-mimic peptide as a molecular trigger of T1D pathogenesis.
Topics: Animals; Autoantibodies; Bacteroidetes; CD8-Positive T-Lymphocytes; Child; Diabetes Mellitus, Type 1; Female; Gastrointestinal Microbiome; Humans; Insulin; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Mimicry; Peptides
PubMed: 35878027
DOI: 10.1073/pnas.2120028119 -
Frontiers in Microbiology 2018Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions,... (Review)
Review
Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions, like the metabolic syndrome (MetS) and it's hepatic manifestation, non-alcoholic fatty liver disease (NAFLD). The intestinal microbial community of obese compared to lean subjects has been shown to undergo configurational shifts in various genera, including but not limited to increased abundances of , and and decreased levels of , and genera. At the phylum level, decreased and increased have been reported. The intestinal microbiota therefore presents an important target for designing novel therapeutic modalities that target extra-intestinal inflammatory disorders, such as NAFLD. This review hypothesizes that disruption of the intestinal-mucosal macrophage interface is a key factor in intestinal-liver axis disturbances. Intestinal immune responses implicated in the manifestation, maintenance and progression of NAFLD provide insights into the dialogue between the intestinal microbiome, the epithelia and mucosal immunity. The pro-inflammatory activity and immune imbalances implicated in NAFLD pathophysiology are reported to stem from dysbiosis of the intestinal epithelia which can serve as a source of hepatoxic effects. We posit that the hepatotoxic consequences of intestinal dysbiosis are compounded through intestinal microbiota-mediated inflammation of the local mucosa that encourages mucosal immune dysfunction, thus contributing important plausible insight in NAFLD pathogenesis. The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD.
PubMed: 29441049
DOI: 10.3389/fmicb.2018.00061 -
Nature Microbiology Sep 2022Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived...
Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived metabolites. Despite the implications for host metabolism, a limited number of specific interactions of the gut microbiome with diet-derived lipids have been characterized. This is partially because obtaining species-level resolution of the responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol-microbiome interactions. Here we performed bio-orthogonal labelling sort sequence spectrometry, a click chemistry based workflow, to profile cholesterol-specific host-microbe interactions. Mice were exposed to an alkyne-functionalized variant of cholesterol and 16S ribosomal RNA gene amplicon sequencing of faecal samples identified diet-derived cholesterol-interacting microbes from the genera Bacteroides, Bifidobacterium, Enterococcus and Parabacteroides. Shotgun metagenomic analysis provided species-level resolution of diet-derived cholesterol-interacting microbes with enrichment of bile acid-like and sulfotransferase-like activities. Using untargeted metabolomics, we identify that cholesterol is converted to cholesterol sulfate in a Bacteroides-specific manner via the enzyme BT_0416. Mice monocolonized with Bacteroides thetaiotaomicron lacking Bt_0416 showed altered host cholesterol and cholesterol sulfate compared with wild-type mice, identifying a previously uncharacterized microbiome-transformation of cholesterol and a mechanism for microbiome-dependent contributions to host phenotype. Moreover, identification of a cholesterol-responsive sulfotransferase in Bacteroides suggests diet-dependent mechanisms for altering microbiome-specific cholesterol metabolism. Overall, our work identifies numerous cholesterol-interacting microbes with implications for more precise microbiome-conscious regulation of host cholesterol homeostasis.
Topics: Animals; Bacteroides; Cholesterol; Cholesterol, Dietary; Dietary Fats; Gastrointestinal Microbiome; Humans; Mice; Microbiota; Sulfotransferases
PubMed: 35982311
DOI: 10.1038/s41564-022-01195-9