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1.
Int J Mol Sci ; 25(8)2024 Apr 11.
Article En | MEDLINE | ID: mdl-38673841

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.


Alopecia Areata , Feces , Gastrointestinal Microbiome , Humans , Alopecia Areata/microbiology , Female , Male , Adult , Feces/microbiology , Cross-Sectional Studies , Dysbiosis/microbiology , Middle Aged , Young Adult , Case-Control Studies , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , RNA, Ribosomal, 16S/genetics , Bacteroides/isolation & purification
2.
Mol Oncol ; 18(5): 1093-1122, 2024 May.
Article En | MEDLINE | ID: mdl-38366793

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.


Bacteroides , Biomarkers, Tumor , Colorectal Neoplasms , Feces , Fusobacterium , Humans , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/diagnosis , Fusobacterium/isolation & purification , Fusobacterium/genetics , Male , Female , Bacteroides/isolation & purification , Bacteroides/genetics , Middle Aged , Feces/microbiology , Faecalibacterium/isolation & purification , Faecalibacterium/genetics , Aged , RNA, Ribosomal, 16S/genetics , Gastrointestinal Microbiome/genetics , Saliva/microbiology , Adult
3.
Article En | MEDLINE | ID: mdl-35805592

Beach sand may act as a reservoir for numerous microorganisms, including enteric pathogens. Several of these pathogens originate in human or animal feces, which may pose a public health risk. In August 2019, high levels of fecal indicator bacteria (FIB) were detected in the sand of the Azorean beach Prainha, Terceira Island, Portugal. Remediation measures were promptly implemented, including sand removal and the spraying of chlorine to restore the sand quality. To determine the source of the fecal contamination, during the first campaign, supratidal sand samples were collected from several sites along the beach, followed by microbial source tracking (MST) analyses of Bacteroides marker genes for five animal species, including humans. Some of the sampling sites revealed the presence of marker genes from dogs, seagulls, and ruminants. Making use of the information on biological sources originating partially from dogs, the municipality enforced restrictive measures for dog-walking at the beach. Subsequent sampling campaigns detected low FIB contamination due to the mitigation and remediation measures that were undertaken. This is the first case study where the MST approach was used to determine the contamination sources in the supratidal sand of a coastal beach. Our results show that MST can be an essential tool to determine sources of fecal contamination in the sand. This study shows the importance of holistic management of beaches that should go beyond water quality monitoring for FIB, putting forth evidence for beach sand monitoring.


Bacteria/isolation & purification , Bathing Beaches/standards , Sand/microbiology , Water Pollution , Animals , Bacteria/classification , Bacteria/genetics , Bacteroides/genetics , Bacteroides/isolation & purification , Charadriiformes , Dogs , Environmental Monitoring/methods , Feces/microbiology , Portugal , Ruminants , Water Microbiology , Water Pollution/analysis
4.
Gut Microbes ; 14(1): 2027853, 2022.
Article En | MEDLINE | ID: mdl-35129072

The intestinal flora plays an important role in the development of many human and animal diseases. Microbiome association studies revealed the potential regulatory function of intestinal bacteria in many liver diseases, such as autoimmune hepatitis, viral hepatitis and alcoholic hepatitis. However, the key intestinal bacterial strains that affect pathological liver injury and the underlying functional mechanisms remain unclear. We found that the gut microbiota from gentamycin (Gen)-treated mice significantly alleviated concanavalin A (ConA)-induced liver injury compared to vancomycin (Van)-treated mice by inhibiting CD95 expression on the surface of hepatocytes and reducing CD95/CD95L-mediated hepatocyte apoptosis. Through the combination of microbiota sequencing and correlation analysis, we isolated 5 strains with the highest relative abundance, Bacteroides acidifaciens (BA), Parabacteroides distasonis (PD), Bacteroides thetaiotaomicron (BT), Bacteroides dorei (BD) and Bacteroides uniformis (BU), from the feces of Gen-treated mice. Only BA played a protective role against ConA-induced liver injury. Further studies demonstrated that BA-reconstituted mice had reduced CD95/CD95L signaling, which was required for the decrease in the L-glutathione/glutathione (GSSG/GSH) ratio observed in the liver. BA-reconstituted mice were also more resistant to alcoholic liver injury. Our work showed that a specific murine intestinal bacterial strain, BA, ameliorated liver injury by reducing hepatocyte apoptosis in a CD95-dependent manner. Determination of the function of BA may provide an opportunity for its future use as a treatment for liver disease.


Bacteroides/physiology , Gastrointestinal Microbiome , Liver Diseases/prevention & control , fas Receptor/metabolism , Animals , Apoptosis , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteroides/genetics , Bacteroides/isolation & purification , Feces/microbiology , Glutathione/metabolism , Hepatocytes/cytology , Hepatocytes/metabolism , Humans , Liver Diseases/metabolism , Liver Diseases/microbiology , Liver Diseases/physiopathology , Mice , Mice, Inbred C57BL , fas Receptor/genetics
5.
Microbiol Spectr ; 9(3): e0125521, 2021 12 22.
Article En | MEDLINE | ID: mdl-34937163

Fecal microbial community could not fully represent the intestinal microbial community. However, most studies analyzing diarrhea-dominant irritable bowel syndrome (IBS-D) were mainly based on fecal samples. We aimed to characterize the IBS-D microbial community patterns using samples at multiple intestinal sites. This study recruited 74 IBS-D patients and 20 healthy controls (HC). 22.34%, 8.51%, 14.89%, and 54.26% of them contributed to one, two, three, and four sites: duodenal mucosa (DM), duodenal lumen (DL), rectal mucosa (RM), and rectal lumen (RL) of intestinal samples, respectively. Then 16S rRNA gene analysis was performed on these 283 samples. The result showed that IBS-D microbial communities have specific patterns at each intestinal site differing from that of HC. Across hosts and sites, Bacillus, Burkholderia, and Faecalibacterium were the representative genera in duodenum of IBS-D, duodenum of HC, and rectum of HC, respectively. Samples from mucosa and lumen in rectum were highly distinguishable, regardless of IBS-D and HC. Additionally, IBS-D patients have lower microbial co-abundance network connectivity. Moreover, RM site-specific biomarker: Bacteroides used alone or together with Prevotella and Oscillospira in RM showed outstanding performance in IBS-D diagnosis. Furthermore, Bacteroides and Prevotella in RM were strongly related to the severity of abdominal pain, abdominal discomfort, and bloating in IBS-D patients. In summary, this study also confirmed fecal microbial community could not fully characterize intestinal microbial communities. Among these site-specific microbial communities, RM microbial community would be more applicable in the diagnosis of IBS-D. IMPORTANCE Microbial community varied from one site to another along the gastrointestinal tract, but current studies about intestinal microbial community in IBS-D were mainly based on fecal samples. Based on 283 intestinal samples collected from DM, DL, RM, and RL of HC and IBS-D, we found different intestinal sites had their site-specific microbial patterns in IBS-D. Notably, RM site-specific microbes Bacteroides, Prevotella, and Oscillospira could be used to discriminate IBS-D from HC accurately. Our findings could help clinicians realize the great potential of the intestinal microbial community in RM for better diagnosis of IBS-D patients.


Duodenum/microbiology , Gastrointestinal Microbiome/genetics , Intestinal Mucosa/microbiology , Irritable Bowel Syndrome/microbiology , Rectum/microbiology , Bacillus/classification , Bacillus/genetics , Bacillus/isolation & purification , Bacteroides/classification , Bacteroides/genetics , Bacteroides/isolation & purification , Burkholderia/classification , Burkholderia/genetics , Burkholderia/isolation & purification , Diarrhea/microbiology , Diarrhea/pathology , Dysbiosis/microbiology , Faecalibacterium/classification , Faecalibacterium/genetics , Faecalibacterium/isolation & purification , Humans , Intestinal Mucosa/pathology , Irritable Bowel Syndrome/pathology , Prevotella/classification , Prevotella/genetics , Prevotella/isolation & purification , RNA, Ribosomal, 16S/genetics
6.
Nat Commun ; 12(1): 5958, 2021 10 13.
Article En | MEDLINE | ID: mdl-34645820

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Allergens/immunology , Food Hypersensitivity/microbiology , Gastrointestinal Microbiome/immunology , Immune Tolerance , Respiratory Hypersensitivity/microbiology , Allergens/adverse effects , Animals , Bacteroides/isolation & purification , Bacteroides/metabolism , Bifidobacterium longum/isolation & purification , Bifidobacterium longum/metabolism , Case-Control Studies , Child , Child, Preschool , Clostridiales/isolation & purification , Clostridiales/metabolism , Dander/adverse effects , Dander/immunology , Eggs/adverse effects , Faecalibacterium prausnitzii/isolation & purification , Faecalibacterium prausnitzii/metabolism , Female , Food Hypersensitivity/etiology , Food Hypersensitivity/immunology , Humans , Lipopolysaccharides/biosynthesis , Male , Milk/adverse effects , Milk/immunology , Nuts/adverse effects , Nuts/immunology , Pollen/chemistry , Pollen/immunology , Prunus persica/chemistry , Prunus persica/immunology , Pyroglyphidae/chemistry , Pyroglyphidae/immunology , Respiratory Hypersensitivity/etiology , Respiratory Hypersensitivity/immunology , Urease/biosynthesis
7.
Sci Rep ; 11(1): 17775, 2021 09 07.
Article En | MEDLINE | ID: mdl-34493783

Macropod progressive periodontal disease (MPPD) is a necrotizing, polymicrobial, inflammatory disease commonly diagnosed in captive macropods. MPPD is characterized by gingivitis associated with dental plaque formation, which progresses to periodontitis and then to osteomyelitis of the mandible or maxilla. However, the underlying microbial causes of this disease remain poorly understood. In this study, we collected 27 oral plaque samples and associated clinical records from 22 captive Macropodidae and Potoroidae individuals that were undergoing clinical examination at Adelaide and Monarto Zoos in South Australia (15 healthy, 7 gingivitis and 5 periodontitis-osteomyelitis samples). The V3-V4 region of the 16S ribosomal RNA gene was sequenced using an Illumina Miseq to explore links between MPPD and oral bacteria in these animals. Compositional differences were detected between the microbiota of periodontitis-osteomyelitis cases compared to healthy samples (p-value with Bonferroni correction < 0.01), as well as gingivitis cases compared to healthy samples (p-value with Bonferroni correction < 0.05) using Permutational Multivariate Analysis of Variance (PERMANOVA). An overabundance of Porphyromonas, Fusobacterium, and Bacteroides taxa was also identified in animals with MPPD compared to healthy individuals using linear discriminant analysis effect size (LEfSe; p = < 0.05). An increased abundance of Desulfomicrobium also was detected in MPPD samples (LEfSe; p < 0.05), which could potentially reflect differences in disease progression. This is the first microbiota analysis of MPPD in captive macropods, and these results support a polymicrobial pathogenesis of MPPD, suggesting that the microbial interactions underpinning MPPD may be more complex than previously documented.


Bacteroides/isolation & purification , Dental Plaque/veterinary , Fusobacterium/isolation & purification , Gingivitis/veterinary , Macropodidae/microbiology , Microbiota , Periodontitis/veterinary , Porphyromonas/isolation & purification , Potoroidae/microbiology , Animals , Animals, Zoo/microbiology , Biodiversity , Coinfection , Dental Plaque/microbiology , Disease Progression , Gingivitis/microbiology , Mandibular Diseases/microbiology , Mandibular Diseases/veterinary , Maxillary Diseases/microbiology , Maxillary Diseases/veterinary , Osteomyelitis/microbiology , Osteomyelitis/veterinary , Periodontitis/microbiology , South Australia
8.
Anaerobe ; 72: 102447, 2021 Dec.
Article En | MEDLINE | ID: mdl-34560274

OBJECTIVES: To assess the differences in antimicrobial susceptibility of UK Bacteroides species across two distinct cohorts from 2000 to 2016. METHODS: Strain identification was performed using matrix-assisted laser-desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) or by partial 16S rRNA sequencing. Minimum inhibitory concentrations (MICs) were determined using agar dilution, following CLSI guidelines (CLSI, 2012; 2017). RESULTS: 224 isolates were included from 2000 to 168 from 2016. Bacteroides fragilis was the most common species, comprising 68% of the 2000 cohort, and 77% in 2016. For all antimicrobials tested, there was an overall increase in the rates of non-susceptible isolates between the cohorts. CONCLUSIONS: The antibiogram of Bacteroides species in the UK is no longer predictable. Multi-drug resistant isolates although rare, are on the rise, and require testing to guide therapy. The monitoring and surveillance of resistance trends is imperative, as is the development of standardised, robust and accessible antimicrobial susceptibility testing methodology for clinical laboratories.


Bacteroides Infections/epidemiology , Bacteroides Infections/microbiology , Bacteroides/classification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Typing Techniques , Bacteroides/drug effects , Bacteroides/isolation & purification , Bacteroides Infections/drug therapy , Bacteroides Infections/history , Drug Resistance, Bacterial/drug effects , History, 21st Century , Humans , Longitudinal Studies , Microbial Sensitivity Tests , Public Health Surveillance , RNA, Ribosomal, 16S/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , United Kingdom/epidemiology
9.
Pharm Biol ; 59(1): 1077-1087, 2021 Dec.
Article En | MEDLINE | ID: mdl-34392792

CONTEXT: Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus db/db mice. However, the mechanism behind this effect has not been reported. OBJECTIVE: To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor. MATERIALS AND METHODS: The normal diet group consisted of db/m mice orally administered 0.2 mL phosphate buffer saline (PBS) (db/m + PBS). For the db/db + PBS (Vehicle) and db/db + KNGT (FMT intervention group) groups, db/db mice received oral 0.2 mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10 weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined. RESULTS: FMT intervention significantly increased the relative abundance of Bacteroides uniformis (0.038%, p < 0.05). Clostridium levels (LogSQ) were increased (p < 0.01), while Mucispirillum schaedleri levels (LogSQ) were decreased (p < 0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68 ± 1.82 mmol/L; 4.13 ± 1.09 mmol/L, p < 0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (p < 0.05). DISCUSSION AND CONCLUSIONS: Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.


Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 2/therapy , Fatty Acids, Volatile/metabolism , Fecal Microbiota Transplantation/methods , Animals , Bacteroides/isolation & purification , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Gastrointestinal Microbiome , Glucagon-Like Peptide 1/metabolism , Glucose Tolerance Test , Glycolipids/metabolism , Humans , Mice , RNA, Ribosomal, 16S , Receptors, G-Protein-Coupled/metabolism
10.
BMC Infect Dis ; 21(1): 625, 2021 Jun 30.
Article En | MEDLINE | ID: mdl-34193073

BACKGROUND: Bacteroides dorei is an anaerobic gram-negative bacterium first described in 2006. Because of the high similarity in mass spectra between B. dorei and Bacteroides vulgatus, discriminating between these species is arduous in clinical practice. In recent decades, 16S rRNA gene sequencing has been a complementary method for distinguishing taxonomically close bacteria, including B. dorei and B. vulgatus, at the genus and species levels. Consequently, B. dorei has been shown to contribute to some diseases, including type 1 autoimmune diabetes mellitus and atherosclerotic diseases. However, there are no reports on invasive infectious diseases caused by B. dorei. This report describes the first case of direct invasion and colonisation of human tissue by B. dorei, thus providing a warning regarding the previously proposed application of B. dorei as a live biotherapeutic for atherosclerotic diseases. CASE PRESENTATION: A 78-year-old Japanese man complained of intermittent chest/back pain and was diagnosed with a mycotic thoracic aortic aneurysm by enhanced computed tomography on admission. Despite strict blood pressure control and empirical antibiotic therapy, the patient's condition worsened. To prevent aneurysmal rupture and eliminate infectious foci, the patient underwent surgical treatment. The resected specimen was subjected to tissue culture and 16S rRNA gene sequencing analysis to identify pathogenic bacteria. A few days after the surgery, culture and sequencing results revealed that the pathogen was B. dorei/B. vulgatus and B. dorei, respectively. The patient was successfully treated with appropriate antibacterial therapy and after improvement, was transferred to another hospital for rehabilitation on postoperative day 34. There was no recurrence of infection or aneurysm after the patient transfer. CONCLUSIONS: This report describes the first case of invasive infectious disease caused by B. dorei, casting a shadow over its utilisation as a probiotic for atherosclerotic diseases.


Aneurysm, Infected/microbiology , Aortic Aneurysm/microbiology , Bacteroides Infections/diagnosis , Bacteroides/isolation & purification , Aged , Aneurysm, Infected/surgery , Aortic Aneurysm/surgery , Humans , Japan/epidemiology , Male , RNA, Ribosomal, 16S , Sequence Analysis, RNA
11.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article En | MEDLINE | ID: mdl-34208885

We previously demonstrated that flavonoid metabolites inhibit cancer cell proliferation through both CDK-dependent and -independent mechanisms. The existing evidence suggests that gut microbiota is capable of flavonoid biotransformation to generate bioactive metabolites including 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA), 3,4,5-trihyroxybenzoic acid (3,4,5-THBA) and 3,4-dihydroxyphenylacetic acid (DOPAC). In this study, we screened 94 human gut bacterial species for their ability to biotransform flavonoid quercetin into different metabolites. We demonstrated that five of these species were able to degrade quercetin including Bacillus glycinifermentans, Flavonifractor plautii, Bacteroides eggerthii, Olsenella scatoligenes and Eubacterium eligens. Additional studies showed that B. glycinifermentans could generate 2,4,6-THBA and 3,4-DHBA from quercetin while F. plautii generates DOPAC. In addition to the differences in the metabolites produced, we also observed that the kinetics of quercetin degradation was different between B. glycinifermentans and F. plautii, suggesting that the pathways of degradation are likely different between these strains. Similar to the antiproliferative effects of 2,4,6-THBA and 3,4-DHBA demonstrated previously, DOPAC also inhibited colony formation ex vivo in the HCT-116 colon cancer cell line. Consistent with this, the bacterial culture supernatant of F. plautii also inhibited colony formation in this cell line. Thus, as F. plautii and B. glycinifermentans generate metabolites possessing antiproliferative activity, we suggest that these strains have the potential to be developed into probiotics to improve human gut health.


3,4-Dihydroxyphenylacetic Acid/pharmacology , Antineoplastic Agents/pharmacology , Bacteria/classification , Bromobenzoates/pharmacology , Gallic Acid/pharmacology , Hydroxybenzoates/pharmacology , Quercetin/chemistry , 3,4-Dihydroxyphenylacetic Acid/chemistry , Actinobacteria/genetics , Actinobacteria/isolation & purification , Actinobacteria/metabolism , Antineoplastic Agents/chemistry , Bacillus/genetics , Bacillus/isolation & purification , Bacillus/metabolism , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Bacterial Proteins , Bacteroides/genetics , Bacteroides/isolation & purification , Bacteroides/metabolism , Bromobenzoates/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Clostridiales/genetics , Clostridiales/isolation & purification , Clostridiales/metabolism , Eubacterium/genetics , Eubacterium/isolation & purification , Eubacterium/metabolism , Gallic Acid/chemistry , Gastrointestinal Microbiome , Gene Expression Profiling , Gene Expression Regulation, Bacterial , HCT116 Cells , Humans , Hydroxybenzoates/chemistry , Phylogeny , Sequence Analysis, RNA
12.
Sci Rep ; 11(1): 13743, 2021 07 02.
Article En | MEDLINE | ID: mdl-34215773

This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.


Colitis, Ulcerative/microbiology , Colon/microbiology , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Adult , Bacteroides/genetics , Bacteroides/isolation & purification , Clostridiales/genetics , Clostridiales/isolation & purification , Colitis, Ulcerative/pathology , Colitis, Ulcerative/therapy , Feces/microbiology , Female , Humans , Intestinal Mucosa/microbiology , Longitudinal Studies , Male , Middle Aged , Prevotella/genetics , Prevotella/isolation & purification , Recurrence
13.
Mol Neurobiol ; 58(10): 4959-4979, 2021 Oct.
Article En | MEDLINE | ID: mdl-34228269

Food addiction (FA) is characterized by behavioral and neurochemical changes linked to loss of food intake control. Gut microbiota may influence appetite and food intake via endocrine and neural routes. The gut microbiota is known to impact homeostatic energy mechanisms, but its role in regulating the reward system is less certain. We show that the administration of Bacteroides uniformis CECT 7771 (B. uniformis) in a rat FA model impacts on the brain reward response, ameliorating binge eating and decreasing anxiety-like behavior. These effects are mediated, at least in part, by changes in the levels of dopamine, serotonin, and noradrenaline in the nucleus accumbens and in the expression of dopamine D1 and D2 receptors in the prefrontal cortex and intestine. B. uniformis reverses the fasting-induced microbiota changes and increases the abundance of species linked to healthy metabolotypes. Our data indicate that microbiota-based interventions might help to control compulsive overeating by modulating the reward response.


Anxiety/metabolism , Bacteroides/metabolism , Binge-Eating Disorder/metabolism , Brain/metabolism , Gastrointestinal Microbiome/physiology , Reward , Animals , Anxiety/therapy , Bacteroides/isolation & purification , Binge-Eating Disorder/therapy , Humans , Infant, Newborn , Male , Microdialysis/methods , Rats , Rats, Inbred WKY
14.
Genome Biol ; 22(1): 187, 2021 06 23.
Article En | MEDLINE | ID: mdl-34162397

BACKGROUND: The human microbiome plays an important role in cancer. Accumulating evidence indicates that commensal microbiome-derived DNA may be represented in minute quantities in the cell-free DNA of human blood and could possibly be harnessed as a new cancer biomarker. However, there has been limited use of rigorous experimental controls to account for contamination, which invariably affects low-biomass microbiome studies. RESULTS: We apply a combination of 16S-rRNA-gene sequencing and droplet digital PCR to determine if the specific detection of cell-free microbial DNA (cfmDNA) is possible in metastatic melanoma patients. Compared to matched stool and saliva samples, the absolute concentration of cfmDNA is low but significantly above the levels detected from negative controls. The microbial community of plasma is strongly influenced by laboratory and reagent contaminants introduced during the DNA extraction and sequencing processes. Through the application of an in silico decontamination strategy including the filtering of amplicon sequence variants (ASVs) with batch dependent abundances and those with a higher prevalence in negative controls, we identify known gut commensal bacteria, such as Faecalibacterium, Bacteroides and Ruminococcus, and also other uncharacterised ASVs. We analyse additional plasma samples, highlighting the potential of this framework to identify differences in cfmDNA between healthy and cancer patients. CONCLUSIONS: Together, these observations indicate that plasma can harbour a low yet detectable level of cfmDNA. The results highlight the importance of accounting for contamination and provide an analytical decontamination framework to allow the accurate detection of cfmDNA for future biomarker studies in cancer and other diseases.


Cell-Free Nucleic Acids/genetics , DNA, Bacterial/genetics , Melanoma/microbiology , Microbiota/genetics , Skin Neoplasms/microbiology , Bacteroides/classification , Bacteroides/genetics , Bacteroides/isolation & purification , Cell-Free Nucleic Acids/blood , DNA Contamination , DNA, Bacterial/blood , Faecalibacterium/classification , Faecalibacterium/genetics , Faecalibacterium/isolation & purification , Feces/microbiology , Humans , Melanoma/diagnosis , Melanoma/pathology , Neoplasm Metastasis , Neoplasm Staging , Polymerase Chain Reaction/methods , RNA, Ribosomal, 16S/genetics , Ruminococcus/classification , Ruminococcus/genetics , Ruminococcus/isolation & purification , Saliva/microbiology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Symbiosis/physiology
15.
J Biosci ; 462021.
Article En | MEDLINE | ID: mdl-34148877

Diagnosis and treatment of various diseases in Ayurveda, the Indian system of medicine, relies on 'prakriti' phenotyping of individuals into predominantly three constitutions, kapha, pitta and vata. Recent studies propose that microbiome play an integral role in precision medicine. A study of the relationship between prakriti - the basis of personalized medicine in Ayurveda and that of gut microbiome, and possible biomarker of an individual's health, would vastly improve precision therapy. Towards this, we analyzed bacterial metagenomes from buccal (oral microbiome) and fecal (gut microbiome) samples of 272 healthy individuals of various predominant prakritis. Major bacterial genera from gut microbiome included Prevotella, Bacteroides and Dialister while oral microbiome included Streptococcus, Neisseria, Veilonella, Haemophilus, Porphyromonas and Prevotella. Though the core microbiome was shared across all individuals, we found prakriti specific signatures such as preferential presence of Paraprevotella and Christensenellaceae in vata individuals. A comparison of core gut microbiome of each prakriti with a database of 'healthy' microbes identified microbes unique to each prakriti with functional roles similar to the physiological characteristics of various prakritis as described in Ayurveda. Our findings provide evidence to Ayurvedic interventions based on prakriti phenotyping and possible microbial biomarkers that can stratify the heterogenous population and aid in precision therapy.


Medicine, Ayurvedic/methods , Metagenome , Precision Medicine/methods , Symbiosis/physiology , Adult , Bacterial Typing Techniques , Bacteroides/classification , Bacteroides/genetics , Bacteroides/isolation & purification , DNA, Bacterial/genetics , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Haemophilus/classification , Haemophilus/genetics , Haemophilus/isolation & purification , Healthy Volunteers , Humans , Male , Mouth/microbiology , Neisseria/classification , Neisseria/genetics , Neisseria/isolation & purification , Phylogeny , Porphyromonas/classification , Porphyromonas/genetics , Porphyromonas/isolation & purification , Prevotella/classification , Prevotella/genetics , Prevotella/isolation & purification , Streptococcus/classification , Streptococcus/genetics , Streptococcus/isolation & purification , Veillonella/classification , Veillonella/genetics , Veillonella/isolation & purification , Veillonellaceae/classification , Veillonellaceae/genetics , Veillonellaceae/isolation & purification
16.
Nature ; 595(7865): 91-95, 2021 07.
Article En | MEDLINE | ID: mdl-34163075

Changing food preferences brought about by westernization that have deleterious health effects1,2-combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods3. Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity4-6. A substantial number of reports have explored the effects of dietary fibre on the gut microbial community7-9. However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.


Dietary Fiber/pharmacology , Feces/microbiology , Gastrointestinal Microbiome/drug effects , Germ-Free Life , Snacks , Adolescent , Adult , Animals , Bacteroides/drug effects , Bacteroides/isolation & purification , Blood Proteins/analysis , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , Obesity/microbiology , Overweight/microbiology , Proteome/analysis , Proteome/drug effects , Young Adult
17.
Gut Microbes ; 13(1): 1-17, 2021.
Article En | MEDLINE | ID: mdl-34132157

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort.Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months.Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota.This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.


Bacteroides/growth & development , Child Development , Gastrointestinal Microbiome , Nervous System/growth & development , Bacteria/classification , Bacteria/genetics , Bacteria/growth & development , Bacteria/isolation & purification , Bacteroides/classification , Bacteroides/genetics , Bacteroides/isolation & purification , Canada , Female , Follow-Up Studies , Humans , Infant , Male , RNA, Ribosomal, 16S/genetics , Retrospective Studies
18.
Nat Commun ; 12(1): 3294, 2021 06 02.
Article En | MEDLINE | ID: mdl-34078892

Experimental manipulation of gut microbes in animal models alters fear behavior and relevant neurocircuitry. In humans, the first year of life is a key period for brain development, the emergence of fearfulness, and the establishment of the gut microbiome. Variation in the infant gut microbiome has previously been linked to cognitive development, but its relationship with fear behavior and neurocircuitry is unknown. In this pilot study of 34 infants, we find that 1-year gut microbiome composition (Weighted Unifrac; lower abundance of Bacteroides, increased abundance of Veillonella, Dialister, and Clostridiales) is significantly associated with increased fear behavior during a non-social fear paradigm. Infants with increased richness and reduced evenness of the 1-month microbiome also display increased non-social fear. This study indicates associations of the human infant gut microbiome with fear behavior and possible relationships with fear-related brain structures on the basis of a small cohort. As such, it represents an important step in understanding the role of the gut microbiome in the development of human fear behaviors, but requires further validation with a larger number of participants.


Bacteroides/genetics , Clostridiales/genetics , Fear/psychology , Gastrointestinal Microbiome/genetics , Veillonella/genetics , Veillonellaceae/genetics , Adult , Bacteroides/classification , Bacteroides/isolation & purification , Brain/physiology , Breast Feeding , Clostridiales/classification , Clostridiales/isolation & purification , Feces/microbiology , Female , Humans , Infant , Infant Formula , Longitudinal Studies , Male , Pilot Projects , RNA, Ribosomal, 16S/genetics , Veillonella/classification , Veillonella/isolation & purification , Veillonellaceae/classification , Veillonellaceae/isolation & purification
19.
Article En | MEDLINE | ID: mdl-33881983

Four unknown strains, characterized as Gram-stain-negative, strictly anaerobic, non-motile and rod-shaped, were isolated from fresh faeces of healthy humans in PR China. Pairwise sequence comparisons of the 16S rRNA genes showed that these isolates were separated into two clusters. Cluster I (strains HF-5141T and HF-106) was most closely related to Bacteroides xylanisolvens XB1AT (98.0-98.3 % similarity) and Bacteroides ovatus ATCC 8483T (97.3-97.5 %), whereas cluster II (strains HF-5287T and HF-5300) exhibited a similarity range of 96.8-97.0 % to Bacteroides finegoldii JCM 13345T, 96.7-96.9 % to Bacteroides faecis MAJ27T and 96.4-96.5 % to Bacteroides xylanisolvens XB1AT. The DNA G+C contents of type strains HF-5141T and HF-5287T were 41.5 and 42.6 mol%, respectively. These strains had anteiso-C15 : 0 as the major cellular fatty acid, MK-9 and MK-11 as the predominant respiratory quinones, and phosphatidylethanolamine, aminophospholipids and phospholipids as major polar lipids, which is typical for members of the genus Bacteroides. However, the average nucleotide identity and digital DNA-DNA hybridization values, accompanied by different phenotypic and biochemical characteristics, distinguished them from their corresponding closest relatives as well as from other recognized members of the genus Bacteroides. Therefore, strains HF-5141T and HF-5287T represent two novel species in the genus Bacteroides, for which the names Bacteroides luhongzhouii sp. nov. and Bacteroides zhangwenhongii sp. nov. are proposed, with HF-5141T (=CGMCC 1.16787T=GDMCC 1.1591T=JCM 33480T) and HF-5287T (=CGMCC 1.16724T=GDMCC 1.1590T=JCM 33481T) as type strains.


Bacteroides/classification , Feces/microbiology , Phylogeny , Bacterial Typing Techniques , Bacteroides/isolation & purification , Base Composition , China , DNA, Bacterial/genetics , Fatty Acids/chemistry , Humans , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/chemistry
20.
PLoS One ; 16(4): e0249944, 2021.
Article En | MEDLINE | ID: mdl-33836012

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that reduces lung and respiratory function, with a high mortality rate. Severe and acute deterioration of COPD can easily lead to respiratory failure, resulting in personal, social, and medical burden. Recent studies have shown a high correlation between the gut microbiota and lung inflammation. In this study, we investigated the relationship between gut microbiota and COPD severity. A total of 60 COPD patients with varying severity according to GOLD guidelines were enrolled in this study. DNA was extracted from patients' stool and 16S rRNA data analysis conducted using high-throughput sequencing followed by bioinformatics analysis. The richness of the gut microbiota was not associated with COPD severity. The gut microbiome is more similar in stage 1 and 2 COPD than stage 3+4 COPD. Fusobacterium and Aerococcus were more abundant in stage 3+4 COPD. Ruminococcaceae NK4A214 group and Lachnoclostridium were less abundant in stage 2-4, and Tyzzerella 4 and Dialister were less abundant in stage 1. However, the abundance of a Bacteroides was associated with blood eosinophils and lung function. This study suggests that no distinctive gut microbiota pattern is associated with the severity of COPD. The gut microbiome could affect COPD by gut inflammation shaping the host immune system.


Bacteria/isolation & purification , Gastrointestinal Microbiome , Pulmonary Disease, Chronic Obstructive/pathology , Aged , Aged, 80 and over , Bacteria/genetics , Bacteroides/genetics , Bacteroides/isolation & purification , Clostridiales/genetics , Clostridiales/isolation & purification , Feces/microbiology , Fusobacterium/genetics , Fusobacterium/isolation & purification , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Severity of Illness Index
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