Intestinal microbiota profiles in a genetic model of colon tumorigenesis correlates with colon cancer biomarkers.

Faecal (FM) and colon mucosal associated microbiota (MAM) were studied in a model of colorectal cancer (CRC), the Apc-mutated Pirc rats, and in age-paired wt F344 rats. Principal Coordinates Analysis indicated that samples' distribution was driven by age, with samples of young rats (1 month old; without tumours) separated from older ones (11-month-old; bearing tumours). Diversity analysis showed significant differences between FM and MAM in older Pirc rats, and between MAM of both Pirc and wt rats and the tumour microbiota, enriched in Enterococcus, Escherichia/Shigella, Proteus and Bifidobacteriaceae. In young animals, Pirc FM was enriched in the genus Delftia, while wt FM was enriched in Lactobacillus and Streptococcus. Some CRC biomarkers and faecal short chain fatty acids (SCFAs) were also measured. Colon proliferation and DClK1 expression, a pro-survival mucosal marker, were higher in Pirc than in wt rats, while the mucin MUC2, was lower in Pirc rats. Branched SCFAs were higher in Pirc than in wt animals. By Spearman analysis CRC biomarkers correlated with FM (in both young and old rats) and with MAM (in young rats), suggesting a specific relationship between the gut microbiota profile and these functional mucosal parameters deserving further investigation.

The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting.

OBJECTIVE: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). METHODS: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. RESULTS: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P = .051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. CONCLUSION: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.

The influence of gut microbiome on progression of overactive bladder symptoms: a community-based 3-year longitudinal study in Aomori, Japan.

PURPOSE: To assess the influence of gut microbiome on overactive bladder (OAB) symptoms progression. METHODS: This was a 3-year longitudinal study, Hirosaki in Japan. We assessed OAB symptoms and reviewed the medication records of each subject in 2016. We extracted 16S rRNA genes from fecal samples and analyzed gut microbiomes via next-generation sequencing. We evaluated the changes in urinary urgency (UU) and/or urgent urinary incontinence (UUI) from 2016 to 2019. We defined UU/UUI-progression as exacerbation of UU and/or UUI. We compared the clinical backgrounds and microbiota structure between UU/UUI-progression subjects and non-progression (controls). We assessed the impact of gut microbiome on the UU/UUI-progression via multivariate logistic regression analyses. RESULTS: Of 669 subjects, 126 were UU/UUI-progression subjects. These subjects had a higher age and prevalence of proton pump inhibitor (PPI) use (14% vs. 5.4%, P = 0.003), irritable bowel syndrome, sleep disturbance, and metabolic syndrome than those without. We found the different microbiota structures between subjects with UU/UUI-progression and those without. A higher relative abundance of genus Streptococcus (harmful bacterial genus for human health) appeared in UU/UUI-progression subjects (3.8% vs. 2.3%, P < 0.001). Multivariate analysis revealed that age ≥ 65 years, current smoking, sleep disturbance, metabolic syndrome, and genus Streptococcus (Odds ratio: 1.05, P = 0.029) were independent risk factors for UU/UUI-progression. PPI use turned to be a significant risk factor on a multivariate analysis without including genus Streptococcus. CONCLUSIONS: Gut microbiome might be associated with a risk for OAB symptoms progression. PPI use might cause gut dysbiosis and increase this risk.

A Multicenter Study of Real-world Practice for Management of Abnormal Liver Function Tests in Children with Acute Infectious Diseases.

BACKGROUND: Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases. Few studies and no definite clinical guidelines for these conditions are available. The present study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea. METHODS: A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L without other specific conditions that could cause ALT elevation. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation. RESULTS: A total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2 ± 274.1 and 194.9 ± 316.1 IU/L (range 23-2,881, 60-2,949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month = 1.003; 95% confidence interval [CI], 1.001-1.004; P = 0.004), while the number of infection episodes (OR = 0.626; 95% CI, 0.505-0.777; P < 0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions. CONCLUSION: Abnormal liver function test after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice.

Dysbiosis of human gut microbiome in young-onset colorectal cancer.

The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.

Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review.

Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent-not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.

Isolation and Identification of Lactic Acid Bacteria from Cow Milk and Milk Products.

Lactic acid bacteria (LAB) have long been consumed by people in several fermented foods such as dairy products. A study was conducted on lactating dairy cows to isolate and characterize LAB from dairy products found in and around Bahir-Dar city, North Western Ethiopia. Milk and milk products were randomly collected from dairy farms, milk vending shops, individual households, and supermarkets for bacteriological investigations. A total of sixteen samples were taken from different sources and cultured on different selective media: de Man, Rogosa, and Sharpe (MRS) agar for Lactobacillus spp.; M17 agar for Lactococcus spp.; Rogasa SL agar for Streptococci spp.; and MRS supplemented with cysteine (0.5%) for Bifidobacteria spp. Different laboratory techniques were implemented for LAB isolation and identification. A total of 41 bacterial isolates were grouped under five different genera of LAB and Bifidobacteria spp. were identified based on the growth morphology on the selective media, growth at a different temperature, gas production from glucose, carbohydrate fermentation, and other biochemical tests. LAB genera such as Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, and Bifidobacterium spp. were isolated and identified from raw milk, cheese, and yogurt. Based on the current study, the majority of the LAB (24.38%) was isolated from cheese and yogurt. Among these, Lactobacillus, Lactococcus (21.94%), Streptococcus (19.51%), Leuconostoc (14.64%), Bifidobacteria (12.19%), and Pediococcus (7.31%) spp. were also identified from these products. Furthermore, based on the bacterial load count and different identification methodologies, our study revealed that Lactobacillus spp. were the dominant LAB isolated from milk and milk products. As a result, since there are few studies on the isolation and identification of lactic acid bacteria from dairy products in Ethiopia, more research studies are needed to complete the identification and characterization to species level and their possible role as probiotics.

Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.

Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.

Streptococcal infection in childhood Henoch-Schönlein purpura: a 5-year retrospective study from a single tertiary medical center in China, 2015-2019.

BACKGROUND: The present study focuses on the associations of streptococcal infection with the clinical phenotypes, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children. METHODS: Two thousand seventy-four Chinese children with HSP were recruited from January 2015 to December 2019. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. Laboratory data of urine tests, blood sample and infectious agents were collected. Renal biopsy was performed by the percutaneous technique. RESULTS: (1) Streptococcal infection was identified in 393 (18.9%) HSP patients, and served as the most frequent infectious trigger. (2) Among the 393 cases with streptococcal infection, 43.0% of them had arthritis/arthralgia, 32.1% had abdominal pain and 29.3% had renal involvement. (3) 26.1% of HSP patients relapsed or recurred more than 1 time within a 5-year observational period, and the relapse/recurrence rate in streptococcal infectious group was subjected to a 0.4-fold decrease as compared with the non-infectious group. (4) No significant differences in renal pathological damage were identified among the streptococcal infectious group, the other infectious group and the non-infectious group. CONCLUSIONS: Streptococcal infection is the most frequent trigger for childhood HSP and does not aggravate renal pathological damage; the possible elimination of streptococcal infection helps relieve the relapse/recurrence of HSP.

Emergency hip disarticulations for severe necrotising fasciitis of the lower limb: a series of rare cases from a rural district general hospital.

Hip disarticulation is the removal of the entire lower limb through the hip joint by detaching the femur from the acetabulum. This major ablative procedure is rarely performed for infection but may be required in severe necrotising fasciitis. We present a single centre retrospective review of all cases of emergency hip disarticulations in patients with necrotising fasciitis between 2010 and 2020. All five patients included in the review presented with acute lower limb pain and sepsis. Three patients had comorbidities predisposing them to necrotising fasciitis. Three were deemed to be high risk and two were at intermediate risk of developing necrotising fasciitis. There were two deaths in the postoperative period. Of the three survivors, two required revision surgery for a completion hindquarter amputation and one for flap closure. All three survivors had good functional outcomes after discharge from hospital. Despite its associated morbidity, emergency amputation of the entire lower limb is a life-saving treatment in cases of rapidly progressing necrotising fasciitis and should be considered as a first-line option in managing this condition.

Commensal microbiota contributes to predicting the response to immune checkpoint inhibitors in non-small-cell lung cancer patients.

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death-1/programmed cell death-ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non-small-cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes' signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti-programmed cell death-1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression-free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor-based immunotherapy.

Extensive Cellulitis and Bacteremia Due to Streptococcus Pseudoporcinus in a Child With Klippel-Trenaunay Syndrome.

Streptococcus pseudoporcinus is a newly recognized ß-hemolytic streptococcus, that is considered a rare pathogen in adults. Infections in children have not been reported. We describe a child with Klippel-Trenaunay syndrome that developed of S. pseudoporcinus cellulitis and bacteremia, which was difficult-to-treat, relapsed and required prolonged antibiotic courses. S. pseudoporcinus can cause invasive infection in children, especially in the presence of predisposing conditions.

Causative bacteria associated with a clinically relevant postoperative pancreatic fistula infection after distal pancreatectomy.

PURPOSE: Clinically relevant postoperative pancreatic fistulas (CR-POPF) occurring after distal pancreatectomy often cause intra-abdominal infections. We monitored the presence of bacterial contamination in the ascitic fluid after distal pancreatectomy to clarify the bacterial origin of intra-abdominal infections associated with CR-POPF. METHODS: In 176 patients who underwent distal pancreatectomy, ascitic fluid bacterial cultures were performed on postoperative days (POD) 1-4 and when the drainage fluid became turbid. The association between postoperative ascitic bacterial contamination and CR-POPF incidence was investigated. RESULTS: CR-POPF occurred in 18 cases (10.2%). Among the patients with CR-POPF, bacterial contamination was detected in 0% on POD 1, in 38.9% on POD 4, and in 72.2% on the day (median, day 9.5) when the drainage fluid became turbid. A univariate analysis revealed a significant difference in ascitic bacterial contamination on POD 4 (p < 0.001) and amylase level on POD 3-4 (p < 0.001). A multivariate analysis revealed the amylase level and ascitic bacterial contamination on POD 4 to be independent risk factors. CONCLUSIONS: In the CR-POPF group, ascitic bacterial contamination was not observed in the early postoperative stage, but the bacterial contamination rate increased after pancreatic juice leakage occurred. Therefore, CR-POPF-related infections in distal pancreatectomy may be caused by a retrograde infection of pancreatic juice.

Quorum Sensing in Streptococcus mutans Regulates Production of Tryglysin, a Novel RaS-RiPP Antimicrobial Compound.

The genus Streptococcus encompasses a large bacterial taxon that commonly colonizes mucosal surfaces of vertebrates and is capable of disease etiologies originating from diverse body sites, including the respiratory, digestive, and reproductive tracts. Identifying new modes of treating infections is of increasing importance, as antibiotic resistance has escalated. Streptococcus mutans is an important opportunistic pathogen that is an agent of dental caries and is capable of systemic diseases such as endocarditis. As such, understanding how it regulates virulence and competes in the oral niche is a priority in developing strategies to defend from these pathogens. We determined that S. mutans UA159 possesses a bona fide short hydrophobic peptide (SHP)/Rgg quorum-sensing system that regulates a specialized biosynthetic operon featuring a radical-SAM (S-adenosyl-l-methionine) (RaS) enzyme and produces a ribosomally synthesized and posttranslationally modified peptide (RiPP). The pairing of SHP/Rgg regulatory systems with RaS biosynthetic operons is conserved across streptococci, and a locus similar to that in S. mutans is found in Streptococcus ferus, an oral streptococcus isolated from wild rats. We identified the RaS-RiPP product from this operon and solved its structure using a combination of analytical methods; we term these RiPPs tryglysin A and B for the unusual Trp-Gly-Lys linkage. We report that tryglysins specifically inhibit the growth of other streptococci, but not other Gram-positive bacteria such as Enterococcus faecalis or Lactococcus lactis We predict that tryglysin is produced by S. mutans in its oral niche, thus inhibiting the growth of competing species, including several medically relevant streptococci.IMPORTANCE Bacteria interact and compete with a large community of organisms in their natural environment. Streptococcus mutans is one such organism, and it is an important member of the oral microbiota. We found that S. mutans uses a quorum-sensing system to regulate production of a novel posttranslationally modified peptide capable of inhibiting growth of several streptococcal species. We find inhibitory properties of a similar peptide produced by S. ferus and predict that these peptides play a role in interspecies competition in the oral niche.

Immunomodulatory streptococci that inhibit CXCL8 secretion and NFκB activation are common members of the oral microbiota.

Introduction. Oral tissues are generally homeostatic despite exposure to many potential inflammatory agents including the resident microbiota. This requires the balancing of inflammation by regulatory mechanisms and/or anti-inflammatory commensal bacteria. Thus, the levels of anti-inflammatory commensal bacteria in resident populations may be critical in maintaining this homeostatic balance.Hypothesis/Gap Statement. The incidence of immunosuppressive streptococci in the oral cavity is not well established. Determining the proportion of these organisms and the mechanisms involved may help to understand host-microbe homeostasis and inform development of probiotics or prebiotics in the maintenance of oral health.Aim. To determine the incidence and potential modes of action of immunosuppressive capacity in resident oral streptococci.Methodology. Supragingival plaque was collected from five healthy participants and supragingival and subgingival plaque from five with gingivitis. Twenty streptococci from each sample were co-cultured with epithelial cells±flagellin or LL-37. CXCL8 secretion was detected by ELISA, induction of cytotoxicity in human epithelial cells by lactate dehydrogenase release and NFκB-activation using a reporter cell line. Bacterial identification was achieved through partial 16S rRNA gene sequencing and next-generation sequencing.Results. CXCL8 secretion was inhibited by 94/300 isolates. Immunosuppressive isolates were detected in supragingival plaque from healthy (4/5) and gingivitis (4/5) samples, and in 2/5 subgingival (gingivitis) plaque samples. Most were Streptococcus mitis/oralis. Seventeen representative immunosuppressive isolates all inhibited NFκB activation. The immunosuppressive mechanism was strain specific, often mediated by ultra-violet light-labile factors, whilst bacterial viability was essential in certain species.Conclusion. Many streptococci isolated from plaque suppressed epithelial cell CXCL8 secretion, via inhibition of NFκB. This phenomenon may play an important role in oral host-microbe homeostasis.

Rare case of osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a postmenopausal woman.

Vertebral osteomyelitis is an infection of the vertebrae that can lead to spinal degeneration, most commonly caused by Staphylococcus aureus Here, we report an unusual case of pyogenic osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a 61-year-old postmenopausal woman. The patient presented with a 2-week history of worsening lower back pain and fever and a recent episode of cystitis following re-engagement of sexual activity. Imaging revealed a deterioration of vertebrae discs and spinal canal stenosis at the L3-L4 levels with a formation of abscess in the right psoas muscle. Needle aspiration of the abscess identified G. vaginalis and S. parasanguinis and the patient was successfully treated with a 6-week course of ceftriaxone and metronidazole. This case describes an unusual coinfection of two pathogens that normally reside in the urogenital tract and oral cavity, respectively, and highlights the risk posed when these organisms breach the body's normal barriers.

Phlegmonous gastritis complicated by abdominal compartment syndrome: a case report.

BACKGROUND: Phlegmonous gastritis (PG) is a rare, suppurative bacterial infection of the gastric wall, which may rapidly evolve into fatal septicemia. The etiology and pathogenesis are poorly understood; however, multiple risk factors have been cited in current literature. Most cases have been diagnosed at autopsy, and occasionally at laparotomy, as the clinical presentation is often variable. CASE PRESENTATION: We report a case of a 67-year-old male presenting with intractable nausea, vomiting, and epigastric pain following an uneventful upper gastrointestinal (GI) endoscopy. Diagnostic workup including contrast tomography (CT) and endoscopic assessment was in keeping with PG. This was subsequently followed by development of abdominal compartment syndrome (ACS) and clinical deterioration necessitating surgical resection of the stomach. CONCLUSION: This case emphasizes the importance of early diagnosis of this potentially fatal infection that can follow endoscopic procedures and illustrates ACS and septic shock as serious complications. There is currently no consensus on the proper management of PG; however, in this case, a combination of surgery and antibiotics provided a favourable outcome. Limited number of cases of PG have been reported in literature, and to our knowledge, this is the first reported case of PG with subsequent ACS as an acute complication.

Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice.

OBJECTIVES: Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the oral microbiota in a prospective cohort of patients with RA, first-degree relatives (FDR) and healthy controls (HC), then genomically and functionally characterised streptococcal species from each group to understand their potential contribution to RA development. METHODS: After DNA extraction from tongue swabs, targeted 16S rRNA gene sequencing and statistical analysis, we defined a microbial dysbiosis score based on an operational taxonomic unit signature of disease. After selective culture from swabs, we identified streptococci by sequencing. We examined the ability of streptococcal cell walls (SCW) from isolates to induce cytokines from splenocytes and arthritis in ZAP-70-mutant SKG mice. RESULTS: RA and FDR were more likely to have periodontitis symptoms. An oral microbial dysbiosis score discriminated RA and HC subjects and predicted similarity of FDR to RA. Streptococcaceae were major contributors to the score. We identified 10 out of 15 streptococcal isolates as S. parasalivarius sp. nov., a distinct sister species to S. salivarius. Tumour necrosis factor and interleukin 6 production in vitro differed in response to individual S. parasalivarius isolates, suggesting strain specific effects on innate immunity. Cytokine secretion was associated with the presence of proteins potentially involved in S. parasalivarius SCW synthesis. Systemic administration of SCW from RA and HC-associated S. parasalivarius strains induced similar chronic arthritis. CONCLUSIONS: Dysbiosis-associated periodontal inflammation and barrier dysfunction may permit arthritogenic insoluble pro-inflammatory pathogen-associated molecules, like SCW, to reach synovial tissue.

Microbiological diagnosis of suspected vertebral osteomyelitis with a focus on the yield of percutaneous needle biopsy: a 10-year cohort study.

This study aims to evaluate in patients hospitalized for vertebral osteomyelitis (VO) the effectiveness of bacteriological diagnosis and the yield of percutaneous needle biopsy (PNB) and to identify factors associated with the result of PNB. This retrospective, two-centre study was conducted between 2000 and 2009. Data on patients with VO were retrieved from the diagnosis database and confirmed by checking medical records. A total of 300 patients with VO were identified; 31 received antibiotics without bacteriological diagnosis, and 269 patients with spondylodiscitis imaging were included. Eighty-three (30.9%) and 18 (6.7%) infections were documented by blood cultures and by bacteriological samples other than PNB, respectively; 168 patients with no bacteriological diagnosis had PNB. Of these, 92 (54.8%) were positive and identified the pathogen and 76 (45.2%) were negative. The most common bacteria were Staphylococcus aureus (34.3%), Streptococcus spp. (20.6%) and coagulase-negative staphylococcus (14.8%). After multivariate analysis, the only factor associated with negative PNB was previous antibiotic intake (OR: 2.31 [1.07-5.00]). When VO was suspected on imaging, bacteriological investigation identified the microorganism in 209/300 (70%) of the cases. The yield of PNB was 54.8%. The only predictor of PNB negativity was previous antibiotic intake. Therefore, we believe that a second PNB should be done after a sufficient delay withdrawal of antibiotics if the first sample was negative. The study was retrospectively registered by the local ethics committee (N°E2019-61).