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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 -
Journal For Immunotherapy of Cancer Jun 20232,5-dimethylcelecoxib (DMC), a derivative of celecoxib, is an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1). Our previous studies have demonstrated that...
BACKGROUND
2,5-dimethylcelecoxib (DMC), a derivative of celecoxib, is an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1). Our previous studies have demonstrated that DMC inhibits the expression of programmed death-ligand 1 on hepatocellular carcinoma (HCC) cells to prevent tumor progression. However, the effect and mechanism of DMC on HCC infiltrating immune cells remain unclear.
METHODS
In this study, single-cell-based high-dimensional mass cytometry was performed on the tumor microenvironment of HCC mice treated with DMC, celecoxib and MK-886 (a known mPGES-1 inhibitor). Moreover, 16S ribosomal RNA sequencing was employed to analyze how DMC improved the tumor microenvironment of HCC by remodeling the gastrointestinal microflora.
RESULTS
We found that (1) DMC significantly inhibited the growth of HCC and improved the prognosis of the mice, and this depended on the stronger antitumor activity of natural killer (NK) and T cells; (2) compared with celecoxib and MK-886, DMC significantly enhanced the cytotoxic and stem-like potential, and inhibited exhaustion of NK and T cells; (3) mechanistically, DMC inhibited the expression of programmed cell death protein-1 and upregulated interferon-γ expression of NK and T cells via the gastrointestinal microbiota (Bacteroides acidifaciens, Odoribacter laneus, and Odoribacter splanchnicus)-AMPK-mTOR axis.
CONCLUSIONS
Our study uncovers the role of DMC in improving the tumor microenvironment of HCC, which not only enriches the relationship between the mPGES-1/prostaglandin E2 pathway and the antitumor function of NK and T cells, but also provide an important strategic reference for multitarget or combined immunotherapy of HCC.Cite Now.
Topics: Animals; Mice; Carcinoma, Hepatocellular; T-Cell Exhaustion; AMP-Activated Protein Kinases; Celecoxib; Gastrointestinal Microbiome; Liver Neoplasms; Dinoprostone; Tumor Microenvironment
PubMed: 37316264
DOI: 10.1136/jitc-2023-006817 -
Frontiers in Cellular and Infection... 2023Globally, liver cancer poses a serious threat to human health and quality of life. Despite numerous studies on the microbial composition of the gut in hepatocellular...
Integrated microbiome and metabolome analysis reveals the interaction between intestinal flora and serum metabolites as potential biomarkers in hepatocellular carcinoma patients.
Globally, liver cancer poses a serious threat to human health and quality of life. Despite numerous studies on the microbial composition of the gut in hepatocellular carcinoma (HCC), little is known about the interactions of the gut microbiota and metabolites and their role in HCC. This study examined the composition of the gut microbiota and serum metabolic profiles in 68 patients with HCC, 33 patients with liver cirrhosis (LC), and 34 healthy individuals (NC) using a combination of metagenome sequencing and liquid chromatography-mass spectrometry (LC-MS). The composition of the serum metabolites and the structure of the intestinal microbiota were found to be significantly altered in HCC patients compared to non-HCC patients. LEfSe and metabolic pathway enrichment analysis were used to identify two key species ( and ) and five key metabolites (ouabain, taurochenodeoxycholic acid, glycochenodeoxycholate, theophylline, and xanthine) associated with HCC, which then were combined to create panels for HCC diagnosis. The study discovered that the diagnostic performance of the metabolome was superior to that of the microbiome, and a panel comprised of key species and key metabolites outperformed alpha-fetoprotein (AFP) in terms of diagnostic value. Spearman's rank correlation test was used to determine the relationship between the intestinal flora and serum metabolites and their impact on hepatocarcinogenesis and progression. A random forest model was used to assess the diagnostic performance of the different histologies alone and in combination. In summary, this study describes the characteristics of HCC patients' intestinal flora and serum metabolism, demonstrates that HCC is caused by the interaction of intestinal flora and serum metabolites, and suggests that two key species and five key metabolites may be potential markers for the diagnosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Gastrointestinal Microbiome; Quality of Life; Metabolome; Biomarkers; Liver Cirrhosis; Biomarkers, Tumor
PubMed: 37260707
DOI: 10.3389/fcimb.2023.1170748 -
Microbiome May 2023Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and...
BACKGROUND
Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women's Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women.
RESULTS
Fusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers.
CONCLUSION
Among women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation. Video Abstract.
Topics: Humans; Female; Gastrointestinal Microbiome; HIV Infections; Carotid Stenosis; Proteomics; Carotid Artery Diseases; Atherosclerosis; Carotid Arteries; Biomarkers; Inflammation
PubMed: 37237391
DOI: 10.1186/s40168-023-01566-2 -
Scientific Reports May 2023Two new bacterial strains, Marseille-P2698 (CSUR P2698 = DSM 103,121) and Marseille-P2260 (CSUR P2260 = DSM 101,844 = SN18), were isolated from human stools...
Two new bacterial strains, Marseille-P2698 (CSUR P2698 = DSM 103,121) and Marseille-P2260 (CSUR P2260 = DSM 101,844 = SN18), were isolated from human stools by the culturomic method. We used the taxonogenomic approach to fully describe these two new bacterial strains. The Marseille-P2698 strain was a Gram-negative, motile, non-spore-forming, rod-shaped bacterium. The Marseille-P2260 strain was a Gram-positive, motile, spore-forming rod-shaped bacterium. Major fatty acids found in Marseille-P2698 were C (63%), C (11%), and C (8%). Those found in Marseille-P2260 strain were C (39%), C (16%) and C (14%). Strains Marseille-P2698 and Marseille-P2260 had 16S rRNA gene sequence similarities of 91.50% with Odoribacter laneus, and of 90.98% and 95.07% with Odoribacter splanchnicus and Eubacterium sulci, respectively. The exhibited digital DNA-DNA Hybridization values lower than 20.7%, and Orthologous Average Nucleotide Identity values lower than 73% compared to their closest related bacterial species O. splanchnicus and E. sulci respectively. Phenotypic, biochemical, phylogenetic, and genomic results obtained by comparative analyses provided sufficient evidence that both of the two studied strains Marseille-P2698 and Marseille-P2260 are two new bacterial species and new bacterial genera for which the names Culturomica massiliensis gen. nov., sp. nov., and Emergencia timonensis gen. nov., sp. nov. were proposed, respectively.
Topics: Humans; Phylogeny; RNA, Ribosomal, 16S; Clostridiales; Gram-Positive Bacteria; Microbiota; Fatty Acids; DNA; DNA, Bacterial; Sequence Analysis, DNA; Bacterial Typing Techniques
PubMed: 37231091
DOI: 10.1038/s41598-023-35443-7 -
Microbiology Spectrum Jun 2023Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most... (Clinical Trial)
Clinical Trial
Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.
Topics: Humans; Bacteria; Colitis, Ulcerative; Communicable Diseases; Fecal Microbiota Transplantation; Feces; Gastrointestinal Microbiome; Treatment Outcome
PubMed: 37093057
DOI: 10.1128/spectrum.04152-22 -
Frontiers in Cellular and Infection... 2023Increasing evidence has supported dysbiosis in the faecal microbiome along control-adenoma-carcinoma sequence. In contrast, the data is lacking for tumor bacterial...
Increasing evidence has supported dysbiosis in the faecal microbiome along control-adenoma-carcinoma sequence. In contrast, the data is lacking for tumor bacterial community over colorectal cancer (CRC) progression, resulting in the uncertainties of identifying CRC-associated taxa and diagnosing the sequential CRC stages. Through comprehensive collection of benign polyps (BP, = 45) and the tumors ( = 50) over the four CRC stages, we explored the dynamics of bacterial communities over CRC progression using amplicons sequencing. Canceration was the primarily factor governing the bacterial community, followed by the CRC stages. Besides confirming known CRC-associated taxa using differential abundance, we identified new CRC driver species based on their keystone features in NetShift, including , and Tumor environments were less selective for stable core community, resulting in heterogeneity in bacterial communities over CRC progression, as supported by higher average variation degree, lower occupancy and specificity compared with BP. Intriguingly, tumors could recruit beneficial taxa antagonizing CRC-associated pathogens at CRC initiation, a pattern known as "cry-for-help". By distinguishing age- from CRC stage-associated taxa, the top 15 CRC stage-discriminatory taxa contributed an overall 87.4% accuracy in diagnosing BP and each CRC stage, in which no CRC patients were falsely diagnosed as BP. The accuracy of diagnosis model was unbiased by human age and gender. Collectively, our findings provide new CRC-associated taxa and updated interpretations for CRC carcinogenesis from an ecological perspective. Moving beyond stratifying case-control, the CRC-stage discriminatory taxa could add the diagnosis of BP and the four CRC stages, especially the patients with poor pathological feature and un-reproducibility between two observers.
Topics: Humans; Biomarkers, Tumor; Reproducibility of Results; Gastrointestinal Microbiome; Colorectal Neoplasms; Bacteria
PubMed: 36992683
DOI: 10.3389/fcimb.2023.1123544 -
Digestive Diseases (Basel, Switzerland) 2023Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease... (Review)
Review
BACKGROUND
Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC).
SUMMARY
While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance toward optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid-producing bacteria, Clostridium clusters IV and XIVa, Odoribacter splanchnicus, and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC.
KEY MESSAGES
There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.
Topics: Humans; Fecal Microbiota Transplantation; Colitis, Ulcerative; Feces; Inflammatory Bowel Diseases; Remission Induction; Treatment Outcome
PubMed: 36858036
DOI: 10.1159/000529591 -
Scientific Reports Dec 2022Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the...
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the pathophysiology of NAFLD through the gut-liver axis. Therefore, we aimed to investigate the genus and species of gut microbiota and their functions in children and adolescents with NAFLD. From May 2017 to July 2018, a total of 58 children and adolescents, including 27 abnormal weight (AW) (obese) NAFLD patients, 16 AW non-NAFLD children, and 15 healthy children, were enrolled in this study at Shenzhen Children's Hospital. All of them underwent magnetic resonance spectroscopy (MRS) to quantify the liver fat fraction. Stool samples were collected and analysed with metagenomics. According to body mass index (BMI) and MRS proton density fat fraction (MRS-PDFF), we divided the participants into BMI groups, including the AW group (n = 43) and the Lean group (n = 15); MRS groups, including the NAFLD group (n = 27) and the Control group (n = 31); and BMI-MRS 3 groups, including NAFLD_AW (AW children with NAFLD) (n = 27), Ctrl_AW (n = 16) (AW children without NAFLD) and Ctrl_Lean (n = 15). There was no difference in sex or age among those groups (p > 0.05). In the BMI groups, at the genus level, Dialister, Akkermansia, Odoribacter, and Alistipes exhibited a significant decrease in AW children compared with the Lean group. At the species level, Megamonas hypermegale was increased in the AW group, while Akkermansia muciniphila, Dialister invisus, Alistipes putredinis, Bacteroides massiliensis, Odoribacter splanchnicus, and Bacteroides thetaiotaomicron were decreased in AW children, compared to the Lean group. Compared with the Control group, the genus Megamonas, the species of Megamonas hypermegale and Megamonas rupellensis, increased in the NAFLD group. Furthermore, the genus Megamonas was enriched in the NAFLD_AW group, while Odoribacter, Alistipes, Dialister, and Akkermansia were depleted compared with the Ctrl_Lean or Ctrl_AW group at the genus level. Megamonas hypermegale and Megamonas rupellensis exhibited a significant increase in NAFLD_AW children compared with the Ctrl_Lean or Ctrl_AW group at the species level. Compared with healthy children, the pathways of P461-PWY contributed by the genus Megamonas were significantly increased in NAFLD_AW. We found that compared to healthy children, the genus Megamonas was enriched, while Megamonas hypermegale and Megamonas rupellensis were enriched at the species level in children and adolescents with NAFLD. This indicates that the NAFLD status and/or diet associated with NAFLD patients might lead to the enrichment of the genus Megamonas or Megamonas species.
Topics: Humans; Adolescent; Child; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Firmicutes; Liver
PubMed: 36539432
DOI: 10.1038/s41598-022-25140-2 -
Food Chemistry Jan 2023At present, uncovering how to preventandcontrol hyperuricemia has become an important public health issue. Fermented traditionalChinesemedicine has exhibited promising...
At present, uncovering how to preventandcontrol hyperuricemia has become an important public health issue. Fermented traditionalChinesemedicine has exhibited promising applications in the clinical management of hyperuricemia. In this study, we generated a hyperuricemic mouse model to explore the potent therapeutic ability of Bacillus subtilis-fermented Astragalus membranaceus (BFA) on this condition by multi-omics analysis. We found that the serum uric acid level was decreased in hyperuricemic mice after BFA treatment. BFA effectively attenuated renal inflammation and regulated the expression of urate transporters. Additionally, we found that BFA could increase the abundances of butyrate-producing bacteria, including Butyricimonas synergistica, Odoribacter splanchnicus, and Collinsella tanakaei, and probiotics, including Lactobacillus intestinalis and Bacillus mycoides, in hyperuricemic mice. Therefore, we believe that BFA has the potential to become a novel safe and valid functional food for addressing hyperuricemia.
Topics: Animals; Astragalus propinquus; Bacillus subtilis; Gastrointestinal Microbiome; Hyperuricemia; Kidney; Mice; Uric Acid
PubMed: 36029678
DOI: 10.1016/j.foodchem.2022.133993