Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis.

Formyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiotherapy. Moreover, rs867228 is associated with accelerated esophageal and colorectal carcinogenesis. Here, we show that dendritic cells from Fpr1-/- mice exhibit reduced migration in response to chemotherapy-treated CRC cells. Moreover, Fpr1-/- mice are particularly susceptible to chronic ulcerative colitis and colorectal oncogenesis induced by the mutagen azoxymethane followed by oral dextran sodium sulfate, a detergent that induces colitis. These experiments were performed after initial co-housing of Fpr1-/- mice and wild-type controls, precluding major Fpr1-driven differences in the microbiota. Pharmacological inhibition of Fpr1 by cyclosporin H also tended to increase intestinal oncogenesis in mice bearing the ApcMin mutation, and this effect was reversed by the anti-inflammatory drug sulindac. We conclude that defective FPR1 signaling favors intestinal tumorigenesis through the modulation of the innate inflammatory/immune response.

Urinary microbiota and bladder cancer: A systematic review and a focus on uropathogens.

The higher incidence of bladder cancer in men has long been attributed to environmental factors, including smoking. The fact that the sex ratio of bladder cancer remains consistently weighted toward men despite the remarkable increase in the prevalence of smoking among women suggests that other risk factors influence the incidence rates of bladder cancer. These factors may include the urinary microbiota. In this study, we provide a review of recent literature regarding the association between bladder cancer and changes in the urinary microbiota, with a focus on the potential role of uropathogens in the microbiota and sex in bladder cancer. Four databases were systematically searched up to 31 March 2021 to identify human case-controlled studies that evaluated the relationship between urinary microbiota and bladder cancer. We combined bacterial taxa that were significantly higher or lower in the bladder cancer group in each study in the urine (voided and catheterized) and tissue samples. Findings from sixteen eligible studies were analyzed. The total sample size of the included studies was 708 participants, including 449 (63.4 %) bladder cancer patients and 259 (36.6 %) participants in the control group. When considering only the taxa that have been reported in at least two different studies, we observed that with regards to neoplastic tissues, no increased taxa were reported, while Lactobacillus (2/5 of the studies on tissue samples) was increased in nonneoplastic-tissue compared to neoplastic-tissues at the genus level. In catheterized urine, Veillonella (2/3 of the studies on catheterized urine) was increased in bladder cancer patients compared to the control groups at the genus level. In voided urine, Acinetobacter, Actinomyces, Aeromonas, Anaerococcus, Pseudomonas, and Tepidomonas were increased in the bladder cancer patients, while Lactobacillus, Roseomonas, Veillonella were increased in the control groups. Regarding gender, the genus Actinotignum was increased in female participants while Streptococcus was increased in male participants at the genus level. Regarding potential uropathogens in the urinary microbiota, Escherichia-Shigella provided conflicting results, with both showing higher and lower levels in the bladder cancer groups. However, the family Enterobacteriaceae was lower in the bladder cancer groups than in the control groups. In conclusion, there is no consensus on what taxa of the urinary microbiota are associated with bladder cancer according to the sample type. Findings on the potential role of uropathogens in the urinary microbiota in bladder cancer remain inconsistent. Due to the limited number of studies, further studies on urinary microbiota and bladder cancer are needed to address this issue. Given that all publications concerning the urinary microbiota and bladder cancer have been performed using 16S rRNA gene sequencing, we propose that polyphasic approaches, including culture-dependent techniques, may allow for a more comprehensive investigation of the urinary microbiota associated with bladder cancer.

Impact of HIV Infection on the Course of Inflammatory Bowel Disease and Drug Safety Profile: A Multicenter GETAID Study.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. METHODS: We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. RESULTS: Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. CONCLUSION: Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.

The Antioxidants Glutathione, Ascorbic Acid and Uric Acid Maintain Butyrate Production by Human Gut Clostridia in The Presence of Oxygen In Vitro.

Uncontrolled oxidative stress, reported in Salmonella and HIV infections, colorectal cancer or severe acute malnutrition, has been associated with anaerobic gut microbiome alteration, impaired butyrate production, mucosal immunity dysregulation and disruption of host-bacterial mutualism. However, the role of major antioxidant molecules in the human body, such as glutathione, ascorbic acid and uric acid, has been neglected in this context. Here, we performed an in vitro metabolomics study of the 3 most odorous anaerobic microbes isolated from the human gut in our laboratory (Clostridium sporogenes, Clostridium subterminale and Romboutsia lituseburensis) when grown in anaerobiosis or in aerobiosis with these 3 antioxidant molecules via gas and liquid chromatography-mass spectrometry (GC/MS and LC/MS). There was no growth or volatile organic compound production in aerobic cultures without the 3 antioxidant molecules. In anaerobiosis, the major metabolic products of the bacteria were thiols, alcohols and short-chain fatty acid esters. The production of alkanes, cycloheptatriene and, paradoxically, increased butyrate production, was observed in the cultures grown in aerobiosis with the 3 antioxidant molecules. The qualitative shift suggests specific molecular mechanisms that remain to be elucidated. The increased production of butyrate, but also isobutyrate and isovalerate in vitro suggests that these 3 antioxidant molecules contributed to the maintenance and active resilience of host-bacterial mutualism against mucosal oxygen and uncontrolled oxidative stress in vivo.

Draft genome and description of Negativicoccus massiliensis strain Marseille-P2082, a new species isolated from the gut microbiota of an obese patient.

Strain Marseille-P2082, an anaerobic, non-motile, asporogenous, Gram-negative, coccoid bacterium was isolated from the faeces of a 33 year-old obese French woman before bariatric surgery. The isolate exhibits 98.65% 16S rRNA gene nucleotide sequence similarity with Negativicoccus succinicivorans strain ADV 07/08/06-B-1388T, its current closest phylogenetic neighbour with standing in nomenclature. However, the dDDH relatedness between the new isolate and N. succinicivorans type strain ADV 07/08/06-B-1388T is 52.5 ± 2.7%. Strain Marseille-P2082 has a genome of 1,360,589 bp with a 51.1% G+C content. Its major fatty acids were identified as C18:1n9, C18:0 and C16:0. Based on its phenotypic, genomic and phylogenetic characteristics, strain Marseille-P2082T [= CSURP2082 (Collection de Souches de l'Unité des Rickettsies) = DSM 100853] is proposed as the type strain of the novel species Negativicoccus massiliensis sp. nov. The 16S rRNA gene sequence and whole-genome shotgun sequence have been deposited in EMBL-EBI under accession numbers LN876651 and LT700188, respectively.

Repertoire of bacterial species cultured from the human oral cavity and respiratory tract.

While the gut microbiota is currently in the spotlight, the airway microbiome has been recently associated with several pulmonary diseases and carcinogenesis. As there are several biases associated with high-throughput sequencing methods, cultivation techniques are crucial for the investigation of the human microbiome. We thus aimed to build an exhaustive database, including a list of microbes isolated by culture from respiratory specimens, by performing a review of the literature. Herein, we have listed a total of 756 species cultured from the human respiratory tract. This represents 27.23% of the overall bacterial richness captured from human being by culture methods. This repertoire could be valuable for the elucidation of the interactions between the respiratory microbiome and human health.

Repertoire of the gut microbiota from stomach to colon using culturomics and next-generation sequencing.

BACKGROUND: Most studies on the human microbiota have analyzed stool samples, although a large proportion of the absorption of nutrients takes place in upper gut tract. We collected samples from different locations along the entire gastrointestinal tract from six patients who had simultaneously undergone upper endoscopy and colonoscopy, to perform a comprehensive analysis using culturomics with matrix assisted laser desorption ionisation - time of flight (MALDI-TOF) identification and by metagenomics targeting the 16S ribosomal ribonucleic acid (rRNA) gene. RESULTS: Using culturomics, we isolated 368 different bacterial species, including 37 new species. Fewer species were isolated in the upper gut: 110 in the stomach and 106 in the duodenum, while 235 were isolated from the left colon (p < 0.02). We isolated fewer aero-intolerant species in the upper gut: 37 from the stomach and 150 from the left colon (p < 0.004). Using metagenomics, 1,021 species were identified. The upper gut microbiota was revealed to be less rich than the lower gut microbiota, with 37,622 reads from the stomach, 28,390 from the duodenum, and 79,047 from the left colon (p < 0.009). There were fewer reads for aero-intolerant species in the upper gut (8,656 in the stomach, 5,188 in the duodenum and 72,262 in the left colon, p < 0.02). Patients taking proton pump inhibitors (PPI) were then revealed to have a higher stomach pH and a greater diversity of species in the upper digestive tract than patients not receiving treatment (p < 0.001). CONCLUSION: Significant modifications in bacterial composition and diversity exist throughout the gastrointestinal tract. We suggest that the upper gut may be key to understanding the relationship between the gut microbiota and health.

Delftia tsuruhatensis, an Emergent Opportunistic Healthcare-Associated Pathogen.

Delftia tsuruhatensis, which was first isolated in environmental samples, was rarely associated with human infections. We report on pneumonia caused by D. tsuruhatensis in an infant who underwent cardiac surgery. Retrospective analyses detected 9 other isolates from 8 patients. D. tsuruhatensis is an emergent pathogen, at least for immunocompromised patients.

Microbiota manipulation for weight change.

Manipulation of the intestinal microbiota has been linked to weight changes and obesity. To explore the influence of specific agents that alter the intestinal flora on weight in different patient groups we conducted a meta-analysis of randomized controlled trials (RCTs) reporting on the effects of probiotics, prebiotics, synbiotics, and antibiotics on weight. We searched the Pubmed and Cochrane Library databases for trials on adults, children, and infants evaluating the effects of these substances on weight. Our primary outcome was weight change from baseline. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. We identified and included 13 adult, 17 children, and 23 infant RCTs. Effects were opposite among adults and children, showing weight loss among adults (SMD -0.54 [-0.83, -0.25)) and minor weight gains among children (SMD 0.20 [0.04, 0.36]) and infants (SMD 0.30 [-0.01, 0.62]) taking mainly Lactobacillus probiotic supplements. Heterogeneity was substantial in the adult and infant analyses and could not be explained by intervention or patient characteristics. Azithromycin administration in children with pulmonary disease was associated with weight gain (SMD 0.39 [0.24, 0.54]), without heterogeneity. A high risk of selective reporting and attrition bias was detected across the studies, making it difficult to draw firm conclusions. Overall, our meta-analysis suggests that there may be a role for probiotics in promoting weight loss in adults and weight gain in children, however additional studies are needed. Though we cannot recommend antibiotic administration for weight manipulation, its use provides advantageous weight gain in children with cystic fibrosis and bronchiectasis.

Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

BACKGROUND: Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. CASE PRESENTATION: A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. CONCLUSIONS: In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

From culturomics to taxonomogenomics: A need to change the taxonomy of prokaryotes in clinical microbiology.

By diversifying culture conditions, in a strategy named culturomics, we were able in a short time to grow 124 new bacterial species from human stools, including 39 strict anaerobes. To describe these microorganisms, we use genome sequencing and MALDI-TOF mass spectrometry. Both tools have been major breakthroughs in clinical microbiology over the past decade, have previously been used for taxonomic purposes, and have the advantage over chemotaxonomic methods and DNA-DNA hybridization, to exhibit an excellent intra- and inter-laboratory reproducibility. We developed a polyphasic taxonomic strategy including MALDI-TOF MS and genomic analyses to describe new bacterial species associated with human beings. This strategy, that we have named taxono-genomics, was used to propose the description of 48 new species, the names of 13 of which have officially been validated. In this manuscript, we briefly reviewed the pros and cons of the currently validated taxonomic tools and propose that genomic sequencing and MALDI-TOF mass spectrometry may be incorporated in the taxonomic classification of prokaryotes.

Kingella kingae DNA in langerhans cell histiocytosis of bone.

Langerhans cell histiocytosis of bone is a rare pediatric neoplastic disorder of unclear pathogenesis. We report the case of a 3-year-old girl who presented with Langerhans cell histiocytosis of the ilium in which Kingella kingae was detected. Our findings argue for the search for K. kingae by polymerase chain reaction in children with Langerhans cell histiocytosis of bone.