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Nature Jul 2022Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key...
Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host, raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared with ancestral and luminal E. gallinarum, mucosally adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and induce increased intestinal and hepatic inflammation. Mechanistically, these changes in bacterial behaviour are associated with non-synonymous mutations or insertion-deletions in defined regulatory genes in E. gallinarum, altered microbial gene expression programs and remodelled cell wall structures. Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.
Topics: Bacteria; Bacterial Translocation; Biological Evolution; Cell Wall; Enterococcus; Gastrointestinal Microbiome; Genomics; Host-Pathogen Interactions; Humans; Inflammation; Intestinal Mucosa; Limosilactobacillus reuteri; Liver; Lymph Nodes; Mutation; Stochastic Processes; Symbiosis
PubMed: 35831502
DOI: 10.1038/s41586-022-04949-x -
Science (New York, N.Y.) Mar 2018Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut...
Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, , to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte- cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. -specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.
Topics: Animals; Anti-Bacterial Agents; Autoantibodies; Autoimmune Diseases; Autoimmunity; Bacterial Translocation; Bacterial Vaccines; DNA, Bacterial; Enterococcus; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Hepatocytes; Humans; Liver; Mice; T-Lymphocytes
PubMed: 29590047
DOI: 10.1126/science.aar7201 -
Nature Communications Jun 2023Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative...
Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.
Topics: Animals; Mice; Cholangitis, Sclerosing; Klebsiella pneumoniae; Phage Therapy; Liver; Inflammation
PubMed: 37277351
DOI: 10.1038/s41467-023-39029-9 -
European Journal of Case Reports in... 2019Endocarditis due to is a rare condition, usually affecting older patients. The most frequent source of infection is the gastrointestinal or genitourinary tracts; it...
UNLABELLED
Endocarditis due to is a rare condition, usually affecting older patients. The most frequent source of infection is the gastrointestinal or genitourinary tracts; it frequently involves the aortic valve and tends to produce heart failure. We present a case of endocarditis developing on a normal native heart valve. is intrinsically resistant to vancomycin. Antibiotic susceptibility patterns indicate that most isolates are penicillin and ampicillin-susceptible.
LEARNING POINTS
Endocarditis due to is rare. is intrinsically resistant to vancomycin.Most isolates are penicillin and ampicillin-susceptible.
PubMed: 30931277
DOI: 10.12890/2019_001054 -
BMC Infectious Diseases May 2018As an opportunistic pathogen, E. gallinarum mainly leads to nosocomial infections, and it's multi-drug resistance has gained more and more attention. Central nervous... (Review)
Review
BACKGROUND
As an opportunistic pathogen, E. gallinarum mainly leads to nosocomial infections, and it's multi-drug resistance has gained more and more attention. Central nervous system infections caused by E. gallinarum are rare, but have been reported more often in recent years. The previous cases were generally secondary to neurosurgery, especially ventriculoperitoneal shunts. In recent years, the cases largely occurred in patients with impaired immune function. The patient in our report may have had dual risk factors (immune impairment and an invasive surgical procedure).
CASE PRESENTATION
The patient, a 35-year-old female, was admitted to our hospital for headaches of 3 days duration accompanied by nausea and vomiting for 2 days. The patient had fevers and chills for 3 days before admission; the peak body temperature was 38.5 °C. The patient had a splenectomy in our hospital 2 years earlier for thrombocytopenia and was thought to be immunocompromised. The abnormal findings on physical examination and laboratory testing were as follows: neck stiffness, present; lumbar puncture: pressure, 300 mmHO; Pandy's test, positive; white blood cell (WBC) count, 1536 × 10/L; monocyte count, 602 × 10/L; monocyte percentage, 39.2%; multinucleate cell count, 934 × 10/L; multinucleate cell percentage, 60.8%; protein, 1.08 g/L; WBC count, 21.1 × 10/ L; neutrophil percentage, 85.3%; neutrophil count, 20.55 × 10/L; C reactive protein (CRP): 136.4 mg/L; procalcitonin, 6.70 ng/mL. The patient was given meropenem (2.0 g, intravenous infusion, every 8 h) for anti-infection supplemented with other symptomatic support treatments. The patient's fever and headache had no significant relief.
CONCLUSIONS
Central nervous system infections caused by E. gallinarum are rare, but should be suspected, particularly inpatients with impaired immune function or ineffective treatment. Avoiding long-term invasive treatment and improving immunity are helpful to reduce the occurrence of E. gallinarum infections. Early detection and diagnosis, as well as rational antibiotic use, are the keys to achieve satisfactory efficacy.
Topics: Adult; Anti-Bacterial Agents; Central Nervous System Infections; Enterococcus; Female; Headache; Humans; Leukocyte Count; Linezolid; Meningitis; Microbial Sensitivity Tests
PubMed: 29783937
DOI: 10.1186/s12879-018-3151-4 -
Bioscience of Microbiota, Food and... 2021We investigated bacteria that have a nutritional symbiotic relationship with respect to milk oligosaccharides in gut microbiota of suckling rats, with specific reference...
We investigated bacteria that have a nutritional symbiotic relationship with respect to milk oligosaccharides in gut microbiota of suckling rats, with specific reference to sialyllactose (SL) degrading . Our next generation sequencing analysis of the colonic contents of 12-day-old suckling rats revealed that almost half of the bacteria in the microbiota belonged to the Lactobacillaceae family. Major species in the contents were identified as , , and . We then monitored changes in numbers of the above species, , and the bacteria belonging to the family Enterobacteriaceae (i.e., enterobacteria) in the colonic contents of infant rats at 7, 12, 21, 28, and 35 days of age by using real-time PCR assays targeting these bacterial groups. The 7-day-old infant rats had a gut microbiota in which enterobacteria were predominant. Such dominance was replaced by and the concomitant markedly increased in those of 12 and 21 days of ages. During this period, the number of enterobacteria declined dramatically, but that of surged dramatically. Our separate experiment showed that supplementation of culture media with SL promoted the growth of and , with marked production of lactic acid. These findings revealed possible milk oligosaccharide-mediated cross-feeding between and , with the former degrading SL to release lactose to be utilized by the latter.
PubMed: 34631332
DOI: 10.12938/bmfh.2021-036 -
BioRxiv : the Preprint Server For... Jul 2023Extraintestinal autoimmune diseases are multifactorial with translocating gut pathobionts implicated as instigators and perpetuators in mice. However, the microbial...
UNLABELLED
Extraintestinal autoimmune diseases are multifactorial with translocating gut pathobionts implicated as instigators and perpetuators in mice. However, the microbial contributions to autoimmunity in humans remain largely unclear, including whether specific pathological human adaptive immune responses are triggered by such pathobionts. We show here that the translocating pathobiont induces human IFNγ Th17 differentiation and IgG3 subclass switch of anti- RNA and correlating anti-human RNA autoantibody responses in patients with systemic lupus erythematosus and autoimmune hepatitis. Human Th17 induction by is cell-contact dependent and involves TLR8-mediated human monocyte activation. In murine gnotobiotic lupus models, translocation triggers IgG3 anti-RNA autoantibody titers that correlate with renal autoimmune pathophysiology and with disease activity in patients. Overall, we define cellular mechanisms of how a translocating pathobiont induces human T- and B-cell-dependent autoimmune responses, providing a framework for developing host- and microbiota-derived biomarkers and targeted therapies in extraintestinal autoimmune diseases.
ONE SENTENCE SUMMARY
Translocating pathobiont promotes human Th17 and IgG3 autoantibody responses linked to disease activity in autoimmune patients.
PubMed: 37425769
DOI: 10.1101/2023.06.29.546430 -
Microbes and Infection 2023The genus Enterococcus is commonly overpopulated in patients with depression compared to healthy control in the feces. Therefore, we isolated Enterococcus faecalis,...
The genus Enterococcus is commonly overpopulated in patients with depression compared to healthy control in the feces. Therefore, we isolated Enterococcus faecalis, Enterococcus durans, Enterococcus gallinarum, Enterococcus faecium, and Enterococcus mundtii from the feces of patients with comorbid inflammatory bowel disease with depression and examined their roles in depression in vivo and in vitro. Of these Enterococci, E. mundtii NK1516 most potently induced NF-κB-activated TNF-α and IL-6 expression in BV2 microglia cells. NK1516 also caused the most potent depression-like behaviors in the absence of sickness behaviors, neuroinflammation, downregulated brain-derived neurotrophic factor (BDNF), and serotonin (5-HT) levels in the hippocampus of mice. Furthermore, E. mundtii NK1516 reduced the mRNA expression of Htr1a in the hippocampus. Its capsular polysaccharide (CP), but not cytoplasmic components, also caused depression-like behaviors and reduced BDNF and serotonin levels in the hippocampus. Conversely, this was not observed with E. mundtii ATCC882, a well-known probiotic, or its CP. Orally gavaged fluorescence isothiocyanate (FITC)-conjugated NK1516 CP was detected in the hippocampus of mice. The NK1516 genome exhibited unique CP biosynthesis-related genes (capD, wbjC, WecB, vioB), unlike that of ATCC882. These findings suggest that E. mundtii may be a risk factor for depression.
Topics: Animals; Humans; Mice; Brain-Derived Neurotrophic Factor; Depression; Down-Regulation; Enterococcus; NF-kappa B; Serotonin
PubMed: 36758891
DOI: 10.1016/j.micinf.2023.105116 -
The Journal of General and Applied... Nov 2022Flavone C-glycosides are not easily degraded because of their strong C-C bond between sugar moieties and aglycones. However, some bacteria such as intestinal species can...
Flavone C-glycosides are not easily degraded because of their strong C-C bond between sugar moieties and aglycones. However, some bacteria such as intestinal species can produce specific enzymes to degrade them. In this study, a bacterial strain P581a, which is capable of deglycosylating flavone C-glycosides, was isolated from human intestinal bacteria and was identified as Enterococcus gallinarum by morphological examination, physiological and biochemical analysis and 16S rRNA gene sequencing. This strain may produce a specific flavonoside glycosidase. The activity of the enzyme in the culture medium containing different quantity of carbon sources was also studied, and it was found that the content of carbon sources is negatively correlated with the deglycosylation efficiency of this strain.
Topics: Humans; RNA, Ribosomal, 16S; Glycosides; Flavones; Bacteria; Carbon
PubMed: 35650022
DOI: 10.2323/jgam.2021.10.002 -
Virus Research Jul 2023Enterococcus gallinarum, a gut pathobiont, is an opportunistic pathogen that carries the risk of antibiotic resistance in the clinic and has been proven to drive...
Enterococcus gallinarum, a gut pathobiont, is an opportunistic pathogen that carries the risk of antibiotic resistance in the clinic and has been proven to drive autoimmunity in both mice and humans. Screening for novel bacteriophages targeting Enterococcus gallinarum is expected to provide a promising strategy for controlling such infections or regulating related chronic diseases. In the present study, we isolated a novel lytic Enterococcus gallinarum phage, Phi_Eg_SY1, which presents favourable thermostability and pH stability. Further assays indicated that Phi_Eg_SY1 can efficiently adsorb and lyse the host bacteria in vitro. Genomic and phylogenetic analyses suggested that Phi_Eg_SY1 does not contain virulence or lysogeny genes and presents a novel unassigned evolutionary lineage among the related dsDNA phages. Phi_Eg_SY1 is therefore considered to be suitable for further applications.
Topics: Humans; Animals; Mice; Bacteriophages; Phylogeny; Enterococcus; Lysogeny
PubMed: 37178793
DOI: 10.1016/j.virusres.2023.199132