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Microbiology Spectrum Aug 2022Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus...
Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and β diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (, , and Roseburia intestinalis) and potential probiotics ( and ) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, sp. 26_22 was negatively associated with serum creatinine ( < 0.05). DN patients could be accurately distinguished from CON by sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by , Fusobacterium varium, and sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.
Topics: Bacteroides; Clostridiales; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gastrointestinal Microbiome; Humans
PubMed: 35863004
DOI: 10.1128/spectrum.00324-22 -
Microbiome Sep 2023Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3....
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome.
RESULTS
We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1β and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3 mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages.
CONCLUSION
These findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL. Video Abstract.
Topics: Animals; Mice; CADASIL; Gastrointestinal Microbiome; Mental Disorders; Cytokines; gamma-Aminobutyric Acid
PubMed: 37684694
DOI: 10.1186/s40168-023-01638-3 -
PloS One 2022Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective...
Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective study to investigate the clinical features of patients with Fusobacterium infections and the differences between infections caused by the species F. necrophorum, F. nucleatum, and F. varium. Additionally, we attempted to identify risk factors for Fusobacterium-associated mortality. This study included all patients at a large tertiary care teaching hospital in South Korea with Fusobacterium infections from January 2006 to April 2021. Demographic, clinical, laboratory, and outcome data were analyzed. Multiple logistic regression analysis was performed to assess the risk factors for in-hospital mortality associated with F. nucleatum and F. varium infections. We identified 272 patients with Fusobacterium infections during the study period. The number of Fusobacterium cases has increased recently, with F. varium infections markedly increasing since 2016 and causing a significant proportion of infections. Patients with F. varium infections were older and had a higher proportion of nosocomial infections than the other groups. The F. nucleatum and F. varium groups showed higher in-hospital mortality than the F. necrophorum group. Through logistic regression analysis, APACHE II score and serum albumin level were considered risk factors for in-hospital mortality. APACHE II score was positively correlated with age, red cell distribution width, and serum blood urea nitrogen, and negatively correlated with serum albumin level. Infections caused by Fusobacterium species are increasing. F. varium causes a significant proportion of severe infections.
Topics: Fusobacterium; Fusobacterium Infections; Humans; Retrospective Studies; Serum Albumin
PubMed: 35421136
DOI: 10.1371/journal.pone.0266610 -
Journal of Animal Science Jan 2023Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant liver abscess-causing Fusobacterium...
Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant liver abscess-causing Fusobacterium necrophorum. However, F. varium was found to be more abundant in the rumen fluid of cattle and under culture conditions tailored to enrich F. necrophorum. Using near-full length 16S ribosomal ribonucleic acid sequencing, we demonstrate that F. varium grows under restrictive conditions commonly used to enumerate F. necrophorum, suggesting that previous F. necrophorum abundance assessment may have been inaccurate and that F. varium may be an underestimated member of the ruminal bacterial community. Fusobacterium varium were not as susceptible as F. necrophorum to in-feed antibiotics conventionally used in feedlots. Exposure to tylosin, the current gold standard for liver abscess reduction strategies in cattle, consistently hindered growth of the F. necrophorum strains tested by over 67% (P < 0.05) relative to the unexposed control. In contrast, F. varium strains were totally or highly resistant (0%-13% reduction in maximum yield, P < 0.05). Monensin, an ionophore antibiotic, had greater inhibitory activity against F. necrophorum than F. varium. Finally, preliminary genomic analysis of two F. varium isolates from the rumen revealed the presence of virulence genes related to those of pathogenic human F. varium isolates associated with active invasion of mammalian cells. The data presented here encourage further investigation into the ecological role of F. varium within the bovine rumen and potential role in liver abscess development, and proactive interventions.
Topics: Humans; Cattle; Animals; Rumen; Fusobacterium; Anti-Bacterial Agents; Liver Abscess; Cattle Diseases; Mammals
PubMed: 37104065
DOI: 10.1093/jas/skad130 -
The FEBS Journal Jul 2011The pathways of glutamate catabolism in the anaerobic bacterium Fusobacterium varium, grown on complex, undefined medium and chemically defined, minimal medium, were...
The pathways of glutamate catabolism in the anaerobic bacterium Fusobacterium varium, grown on complex, undefined medium and chemically defined, minimal medium, were investigated using specifically labelled (13)C-glutamate. The metabolic end-products acetate and butyrate were isolated from culture fluids and derivatized for analysis by nuclear magnetic resonance and mass spectrometry. On complex medium, labels from L-[1-(13)C]glutamate and L-[4-(13)C]glutamate were incorporated into C1 of acetate and equally into C1/C3 of butyrate, while label derived from L-[5-(13)C]glutamate was not incorporated. The isotopic incorporation results and the detection of glutamate mutase and 3-methylaspartate ammonia lyase in cell extracts are most consistent with the methylaspartate pathway, the best known route of glutamate catabolism in Clostridium species. When F. varium was grown on defined medium, label from L-[4-(13)C]glutamate was incorporated mainly into C4 of butyrate, demonstrating a major role for the hydroxyglutarate pathway. Upon addition of coenzyme B(12) or cobalt ion to the defined medium in replicate experiments, isotope was located equally at C1/C3 of butyrate in accord with the methylaspartate pathway. Racemization of D-glutamate and subsequent degradation of L-glutamate via the methylaspartate pathway are supported by incorporation of label into C2 of acetate and equally into C2/C4 of butyrate from D-[3-(13)C]glutamate and the detection of a cofactor-independent glutamate racemase in cell extracts. Together the results demonstrate a major role for the methylaspartate pathway of glutamate catabolism in F. varium and substantial participation of the hydroxyglutarate pathway when coenzyme B(12) is not available.
Topics: Acetic Acid; Amino Acid Isomerases; Ammonia-Lyases; Bacterial Proteins; Butyrates; Carbon Isotopes; Chromatography, High Pressure Liquid; Cobalt; Cobamides; Fusobacterium; Glutamic Acid; Glutarates; Intramolecular Transferases; Kinetics; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Weight; N-Methylaspartate; Stereoisomerism
PubMed: 21575137
DOI: 10.1111/j.1742-4658.2011.08179.x -
Scientific Reports Jun 2022Fusobacteria have been suspected to be pathobionts of colon cancer and inflammatory bowel disease. However, the immunomodulatory properties that affect these...
Fusobacteria have been suspected to be pathobionts of colon cancer and inflammatory bowel disease. However, the immunomodulatory properties that affect these inflammatory reactions in dendritic cells (DCs) under anaerobic and aerobic conditions have not yet been characterized. We directly assessed the stimulatory effects of anaerobic commensal bacteria, including fusobacteria, on a human DC line through coculture under aerobic or anaerobic conditions. Under aerobic or anaerobic conditions, stimulation of the DC line with all live commensal bacteria examined, except the probiotic Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus), significantly increased the geometric mean fluorescent intensity (MFI) of marker proteins (HLA-ABC, HLA-DR, CD80, CD86, CD83, or CCR7) on the DC surface. In particular, both Fusobacterium nucleatum (F. nucleatum) and Escherichia coli (E. coli) significantly increased the expression of DC-associated molecules, except for CD83 under both aerobic and anaerobic conditions. The DC line stimulated with Fusobacterium varium (F. varium) significantly increased only CD80, HLA-ABC, and HLA-DR expression under anaerobic conditions. Moreover, differences in the levels of proinflammatory cytokines, such as IL-6, IL-8, and TNF-α, were detected in the DC line stimulated by all live commensal bacteria under either aerobic or anaerobic conditions. Under aerobic conditions, the DC line stimulated with E. coli produced significantly more IL-6, IL-8, and TNF-α than did the cells stimulated with any of the bacteria examined. When E. coli were used to stimulate the DC line under anaerobic conditions, TNF-α was predominantly produced compared to stimulation with any other bacteria. Compared to the DC line stimulated with any other bacteria, the cells stimulated with F. nucleatum showed significantly increased production of IL-6, IL-8 and TNF-α only under anaerobic conditions. In particular, E. coli, F. nucleatum, and F. varium strongly stimulated the DC line, resulting in significantly increased expression of surface molecules associated with DCs and production of inflammatory cytokines.
Topics: Anaerobiosis; B7-1 Antigen; Cells, Cultured; Cytokines; Dendritic Cells; Escherichia coli; Fusobacteria; HLA-DR Antigens; Humans; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha
PubMed: 35739324
DOI: 10.1038/s41598-022-14934-z -
Journal of Clinical Microbiology Aug 2005Bacteremia due to Fusobacterium spp. is unusual (<10% of cases of anaerobic bacteremia), and the isolation of Fusobacterium varium is especially uncommon. The most... (Review)
Review
Bacteremia due to Fusobacterium spp. is unusual (<10% of cases of anaerobic bacteremia), and the isolation of Fusobacterium varium is especially uncommon. The most probable sources of Fusobacterium bacteremia are the respiratory, the gastrointestinal, and the genitourinary tracts. A.-M. Bourgault et al. (Clin. Infect. Dis. 25[Suppl. 2]:181-183) described 40 patients with Fusobacterium bacteremia; only 3 had Fusobacterium varium, and no one had decubitus scars as the portal of entry. In another published series (S. Henry, A. De Maria, and W. R. McCabe, Am. J. Med. 75:225-231, 1983) of 26 cases, two patients had concomitant pulmonary lesions and decubitus ulcers but there was no identification to the species level mentioned. We report a case of Fusobacterium varium bacteremia and infected sacral decubitus ulcer in an elderly patient.
Topics: Aged; Bacteremia; Clindamycin; Drug Resistance, Bacterial; Female; Fusobacterium; Fusobacterium Infections; Humans; Pressure Ulcer
PubMed: 16082005
DOI: 10.1128/JCM.43.8.4293-4295.2005 -
PloS One 2017Fusobacterium spp. present in the oral and gut flora is carcinogenic and is associated with the risk of pancreatic and colorectal cancers. Fusobacterium spp. is also...
Fusobacterium spp. present in the oral and gut flora is carcinogenic and is associated with the risk of pancreatic and colorectal cancers. Fusobacterium spp. is also implicated in a broad spectrum of human pathologies, including Crohn's disease and ulcerative colitis (UC). Here we report the complete genome sequence of Fusobacterium varium Fv113-g1 (genome size, 3.96 Mb) isolated from a patient with UC. Comparative genome analyses totally suggested that Fv113-g1 is basically assigned as F. varium, in particular, it could be reclassified as notable F. varium subsp. similar to F. ulcerans because of partial shared orthologs. Compared with the genome sequences of F. varium ATCC 27725 (genome size, 3.30 Mb) and other strains of Fusobacterium spp., Fv113-g1 possesses many accessary pan-genome sequences with noteworthy multiple virulence factors, including 44 autotransporters (type V secretion system, T5SS) and 13 Fusobacterium adhesion (FadA) paralogs involved in potential mucosal inflammation. Indeed, transcriptome analysis demonstrated that Fv113-g1-specific accessary genes, such as multiple T5SS and fadA paralogs, showed notably increased expression with D-MEM cultivation than with brain heart infusion broth. This implied that growth condition may enhance the expression of such potential virulence factors, leading to remarkable survival against other gut microorganisms and to the pathogenicity to human intestinal epithelium.
Topics: Bacterial Proteins; Colitis, Ulcerative; Fusobacterium; Genome, Bacterial; Humans; Transcriptome
PubMed: 29216329
DOI: 10.1371/journal.pone.0189319 -
Frontiers in Neuroscience 2022To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
OBJECTIVE
To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
METHODS
Patients with ages > 18 years were consecutively enrolled from the outpatient department, Affiliated Hospital of Guizhou Medical University from January 2018 to December 2019. A total of 71 subjects were recruited, including epilepsy patients ( = 41) as an observation group and patient family members ( = 30) as a control group. Fresh stool specimens of all the subjects were collected. The 16S ribosomal RNA sequencing was analyzed to determine changes in intestinal flora composition and its correlation with epilepsy. Subgroup analysis was then conducted. All patients with epilepsy were divided into an urban group ( = 21) and a rural group ( = 20) according to the region, and bioinformatics analyses were repeated between subgroups.
RESULTS
LEfSe analysis showed that , , , and had relatively increased abundance in the epilepsy group at the genus level. Correlation analysis suggested that sp. ( = 0.584, < 0.01), ( = 0.560, < 0.01), ( = 0.541, < 0.01), and ( = 0.506, < 0.01) were significantly positively correlated with the occurrence of epilepsy ( ≥ 0.5, < 0.05). PICRUSt function prediction analysis showed that there were significant differences in 16 pathways between the groups at level 3. Comparing the rural group with the urban group, increased at the phylum level and , , , and increased at the species level in the rural group.
CONCLUSION
There were significant differences in the composition and functional pathways of gut flora between epilepsy patients and patient family members. The may become a potential biomarker for the diagnosis of epilepsy.
PubMed: 35250450
DOI: 10.3389/fnins.2022.803538 -
BMJ Case Reports Oct 2019We present a very rare case of concurrent empyema and liver abscess caused by Fusobacterium. Our patient presented with 3-month history of subtle abdominal discomfort... (Review)
Review
We present a very rare case of concurrent empyema and liver abscess caused by Fusobacterium. Our patient presented with 3-month history of subtle abdominal discomfort and cough leading to eventually presenting with marked chest pain, dyspnoea and septic shock. CT revealed a liver abscess and large right-sided pleural effusion. Drainage of the pleural effusion yielded gross pus with the growth of , while drainage of the liver abscess yielded The patient responded to drainage and antibiotic therapy with resolution of symptoms and decrease in the size of empyema and abscess on follow-up imaging. We also include a review if literature of related fusobacterial infections.
Topics: Empyema, Pleural; Fusobacterium; Fusobacterium Infections; Humans; Liver Abscess, Pyogenic; Male; Middle Aged
PubMed: 31615779
DOI: 10.1136/bcr-2019-231994