The human intestinal bacterium Eggerthella lenta influences gut metabolomes in gnotobiotic mice.

The intestinal microbiota and its metabolites are known to influence host metabolic health. However, little is known about the role of specific microbes. In this work, we used the minimal consortium Oligo-Mouse-Microbiota (OMM12) to study the function of Coriobacteriia under defined conditions in gnotobiotic mice. OMM12 mice with or without the addition of the dominant gut bacterium Eggerthella lenta (E. lenta) were fed with diets varying in fat content and primary bile acids. E. lenta stably colonised the mouse caecum at high relative abundances (median: 27.5%). This was accompanied by decreased occurrence of Akkermansia muciniphila and Enterococcus faecalis, but results did not reach statistical significance in all groups depending on diet and inter-individual differences. Changes in host parameters (anthropometry, blood glucose, and cholesterol) and liver proteomes were primarily due to diet. In contrast, metabolomes in colon content differed significantly between the colonisation groups. The presence of E. lenta was associated with elevated levels of latifolicinin C acid and decreased creatine, sarcosine, N,N-dimethylarginine, and N-Acetyl-DL-methionine. In conclusion, E. lenta altered specific metabolites in the colon but did not have significant effects on the mice or liver proteomes under the conditions tested due to marked inter-individual differences.

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.

Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.

First periprosthetic hip infection caused by Eggerthella lenta.

Periprosthetic joint infection (PJI) caused by anaerobic, Gram-positive bacilli is rare. We present here a case of an 83-year-old female patient who was admitted to our tertiary referral arthroplasty center to treat a complex PJI of her right hip joint after multiple failed surgeries. External and intraoperative cultures reveald growth of Eggerthella lenta (E. lenta). Microbiological identification was fast but in a very few samples. A successful management, comprising of radical debridement with one-stage exchange and an antibiotic treatment with multiple antibiotics, has been achieved at 24-month follow-up. To the best of our knowledge, we have provided the first case study of a hip PJI caused by E. lenta successfully treated with one-stage exchange and an adequate antibiotic treatment.

Relationship Between Gut Bacteria and Levodopa Metabolism.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by the reduction of dopamine neurons in the substantia nigra. Levodopa, as a dopamine supplement, is the gold-standard therapeutic drug for PD. The metabolism of levodopa in the periphery not only decreases its bioavailability but also affects its efficacy. Thus, it is necessary to investigate how levodopa is metabolized. A growing number of studies have shown that intestinal bacteria, such as Enterococcus faecalis, Eggerthella lenta and Clostridium sporogenes, could metabolize levodopa in different ways. In addition, several pathways to reduce levodopa metabolism by gut microbiota were confirmed to improve levodopa efficacy. These pathways include aromatic amino acid decarboxylase (AADC) inhibitors, antibiotics, pH and (S)-α-fluoromethyltyrosine (AFMT). In this review, we have summarized the metabolic process of levodopa by intestinal bacteria and analyzed potential approaches to reduce the metabolism of levodopa by gut microbiota, thus improving the efficacy of levodopa.

Rapidly Progressive Malignant Pelvic Perivascular Epithelioid Cell Neoplasm (PEComa) Associated with Eggerthella lenta Bloodstream Infection.

Perivascular epithelioid cell tumors (PEComa) are rare mesenchymal neoplasms composed of cells that express melanocytic and myogenic markers and grow around small blood vessels. PEComa often show benign behaviors but can also be highly aggressive. In frail and more complex patients, many conditions can overlap, compounding the diagnostic and therapeutic difficulties inherent in rare diseases. Moreover, the complexity of modern patients introduces new and significant players in host-microbe interactions, and emerging pathogens represent a relevant challenge to modern healthcare. Among these pathogens is Eggerthella lenta, an anaerobic gram-positive bacterium of the normal gut microbiota associated with life-threatening infections. Here, we present a case of malignant pelvic PEComa with rapid metastatic progression in a 73-year-old man who presented with an E. lenta bloodstream infection. Approaching differential diagnosis with open-mindedness may assist in better imaging interpretation, surgery scheduling, and proper treatment planning. The non-specific clinical presentation might delay timely diagnosis, while the absence of well-consolidated guidelines undermines the accurate management of the disease, for which strict follow-up can favor better outcomes. Progress in diagnostic techniques, such as the implementation of MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) mass spectrometry for micro-organism identification, helps with a more accurate pathogen diagnosis and characterization. This allows the implementation of the most appropriate therapy, as well as better surveillance of antibiotic resistance, infection prevention, and control measures. Nevertheless, a good dose of wisdom is vital to avoid overlooking potentially harmful pathogens, particularly in frail individuals.

Eggerthella lenta DSM 2243 Alleviates Bile Acid Stress Response in Clostridium ramosum and Anaerostipes caccae by Transformation of Bile Acids.

Bile acids are crucial for the uptake of dietary lipids and can shape the gut-microbiome composition. This latter function is associated with the toxicity of bile acids and can be modulated by bile acid modifying bacteria such as Eggerthella lenta, but the molecular details of the interaction of bacteria depending on bile acid modifications are not well understood. In order to unravel the molecular response to bile acids and their metabolites, we cultivated eight strains from a human intestinal microbiome model alone and in co-culture with Eggerthella lenta in the presence of cholic acid (CA) and deoxycholic acid (DCA). We observed growth inhibition of particularly gram-positive strains such as Clostridium ramosum and the gram-variable Anaerostipes cacae by CA and DCA stress. C. ramosum was alleviated through co-culturing with Eggerthella lenta. We approached effects on the membrane by zeta potential and genotoxic and metabolic effects by (meta)proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta decreased both CA and DCA by the formation of oxidized and epimerized bile acids. Eggerthella lenta also produces microbial bile salt conjugates in a co-cultured species-specific manner. This study highlights how the interaction with other bacteria can influence the functionality of bacteria.

Polymicrobial anaerobic sepsis due to Bacteroides fragilis, Eggerthella lenta, Ruminoccocus gnavus, and Bilophila wadsworthia in a patient with myeloproliferative neoplasm.

We report a rare case of polymicrobial anaerobic bacteremia caused by four different gut anaerobes: Bacteroides fragilis, Eggerthella lenta, Bilophila wadsworthia, and Ruminococcus gnavus. Early initiation of appropriate therapy and species identification with matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) resulted in full recovery from the infection. Our case highlights the clinical significance of polymicrobial cultures and the importance of performing anaerobic cultures for blood specimens to ensure proper identification and treatment.

Morphological and Genetic Characterization of Eggerthella lenta Bacteriophage PMBT5.

Eggerthella lenta is a common member of the human gut microbiome. We here describe the isolation and characterization of a putative virulent bacteriophage having E. lenta as host. The double-layer agar method for isolating phages was adapted to anaerobic conditions for isolating bacteriophage PMBT5 from sewage on a strictly anaerobic E. lenta strain of intestinal origin. For this, anaerobically grown E. lenta cells were concentrated by centrifugation and used for a 24 h phage enrichment step. Subsequently, this suspension was added to anaerobically prepared top (soft) agar in Hungate tubes and further used in the double-layer agar method. Based on morphological characteristics observed by transmission electron microscopy, phage PMBT5 could be assigned to the Siphoviridae phage family. It showed an isometric head with a flexible, noncontractile tail and a distinct single 45 nm tail fiber under the baseplate. Genome sequencing and assembly resulted in one contig of 30,930 bp and a mol% GC content of 51.3, consisting of 44 predicted protein-encoding genes. Phage-related proteins could be largely identified based on their amino acid sequence, and a comparison with metagenomes in the human virome database showed that the phage genome exhibits similarity to two distantly related phages.

Identification and Antibiotic Susceptibility of Eggerthella lenta in Bloodstream Infections.

The identification and antibiotic susceptibility of two clinical isolates of Eggerthella lenta from bloodstream infections were determined. This microorganism is rarely pathogenic, and the findings are presented here to promote the detection and awareness of this infection. The bacteria were obtained from one patient with pressure sores and another with a malignant gastric tumor. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, MALDI-TOF MS, and the 16S rRNA gene sequencing. Antibiotic sensitivity was assessed by the agar dilution method. The bacilli were found to be Gram-positive, and the MS results showed 99.8% homology with E. lenta. It was confirmed by gene sequencing. Antibiotic susceptibility tests demonstrated that E. lenta was sensitive to piperacillin-tazobactam, ampicillin-sulbactam, imipenem, meropenem, metronidazole, clindamycin, and vancomycin. This study could increase awareness of this rare infection.

Selective Isolation of Eggerthella lenta from Human Faeces and Characterisation of the Species Prophage Diversity.

Eggerthella lenta is an anaerobic, high GC, Gram-positive bacillus commonly found in the human digestive tract that belongs to the class Coriobacteriia of the phylum Actinobacteria. This species has been of increasing interest as an important player in the metabolism of xenobiotics and dietary compounds. However, little is known regarding its susceptibility to bacteriophage predation and how this may influence its fitness. Here, we report the isolation of seven novel E. lenta strains using cefotaxime and ceftriaxone as selective agents. We conducted comparative and pangenome analyses of these strains and those publicly available to investigate the diversity of prophages associated with this species. Prophage gene products represent a minimum of 5.8% of the E. lenta pangenome, comprising at least ten distantly related prophage clades that display limited homology to currently known bacteriophages. All clades possess genes implicated in virion structure, lysis, lysogeny and, to a limited extent, DNA replication. Some prophages utilise tyrosine recombinases and diversity generating retroelements to generate phase variation among targeted genes. The prophages have differing levels of sensitivity to the CRISPR/cas systems of their hosts, with spacers from 44 E. lenta isolates found to target only five out of the ten identified prophage clades. Furthermore, using a PCR-based approach targeting the prophage attP site, we were able to determine that several of these elements can excise from the host chromosome, thus supporting the notion that these are active prophages. The findings of this study provide further insights into the diversity of prophages infecting species of the phylum Actinobacteria.

The influence of the gut microbiome on BCG-induced trained immunity.

BACKGROUND: The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown. RESULTS: Stool and blood were collected from 321 healthy adults before BCG vaccination, followed by blood sampling after 2 weeks and 3 months. Metagenomics based on de novo genome assembly reveals 43 immunomodulatory taxa. The nonspecific, trained immune response is detected by altered production of cytokines IL-6, IL-1ß, and TNF-α upon ex vivo blood restimulation with Staphylococcus aureus and negatively correlates with abundance of Roseburia. The specific response, measured by IFN-γ production upon Mycobacterium tuberculosis stimulation, is associated positively with Ruminococcus and Eggerthella lenta. The identified immunomodulatory taxa also have the strongest effects on circulating metabolites, with Roseburia affecting phenylalanine metabolism. This is corroborated by abundances of relevant enzymes, suggesting alternate phenylalanine metabolism modules are activated in a Roseburia species-dependent manner. CONCLUSIONS: Variability in cytokine production after BCG vaccination is associated with the abundance of microbial genomes, which in turn affect or produce metabolites in circulation. Roseburia is found to alter both trained immune responses and phenylalanine metabolism, revealing microbes and microbial products that may alter BCG-induced immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination.

Eggerthella lenta bacteremia successfully treated with ceftizoxime: case report and review of the literature.

Eggerthella lenta is a normal human microflora that is anaerobic, non-sporulating, and Gram positive. However, an increasing number of studies have shown that it could also be an important pathogen for humans, even causing life-threatening infection under certain conditions. However, understanding its pathogenic mechanism and treatment options still need to be improved; more clinical data are needed to explore it further. In this article, we report a case of ceftizoxime-cured E. lenta bacteremia and review the recent literature to provide more clinical data for the diagnosis of E. lenta bacteremia. Our report suggests that the frequency of E. lenta bacteremia is increased in patients with hematologic or solid organ cancer, diabetes mellitus and also in those with appendicitis.

Eggerthella lenta Bacteremia in a Middle-Aged Healthy Man with Acute Hepatic Abscess: Case Report and Literature Review, 1970-2020.

Eggerthella lenta (E. lenta) is a rare but significant human emerging pathogen. Infections caused by it are rare and little-known, both on clinical and therapeutical aspects, in spite of new emergence of bacteria isolation and identification techniques. In this article, we report a case involving a previously healthy 52-year-old man suffering from a newly diagnosed hepatic abscess who developed E. lenta bacteremia, which was treated successfully using empirical therapy with ertapenem and teicoplanin. To the best of our knowledge, this is the first documented report of E. lenta bacteremia related specifically to liver abscess. Cases related to this bacterial species are infrequent and sporadic; thus, we reviewed English literature on E. lenta infection in PubMed/MEDLINE in the last 50 years. A total of 31 sporadic cases were identified. The majority of patients were male (71%), had an average age of 54.3 years and presented predisposing conditions, such as digestive system trouble (45.2%), immunocompromised state (25.8%) or risk factors (22.6%). Two of the cases had more than one predisposing factors. Fever was common (93.5%). Average days to diagnosis of them were 6.8 days. MALDI-TOF MS is emerging as a fast and useful tool in the identification of it. Teicoplanin, vancomycin, amoxicillin-clavulanate, metronidazole, clindamycin, cefoxitin, chloramphenicol, and carbapenems appear to be the most used antibiotic treatment options. The purpose of this review is to increase awareness about the clinical infections caused by E. lenta.

Antimicrobial susceptibility testing of Eggerthella lenta blood culture isolates at a university hospital in Belgium from 2004 to 2018.

OBJECTIVES: Eggerthella lenta is a Gram-positive anaerobic bacillus that is an important cause of bloodstream infections. This study aims to test the susceptibility of Eggerthella lenta blood culture isolates to commonly used antibiotics for the empirical treatment of anaerobic infections. METHODS: In total, 49 positive blood cultures for Eggerthella lenta were retrospectively included from patients hospitalised at the Universitair Ziekenhuis Brussel, Belgium, between 2004 and 2018. Identification was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Antimicrobial susceptibility testing was performed using the reference agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines with Brucella agar supplemented with 5 µg/mL hemin, 1 µg/mL vitamin K1 and 5% laked sheep blood. The minimal inhibitory concentrations were interpreted using the EUCAST breakpoints. Clinical characteristics were collected by reviewing the patient's medical records. RESULTS: All isolates were susceptible to amoxicillin-clavulanate, metronidazole and meropenem. Eighty-eight % of them were susceptible to clindamycin and 94% (20% S, 74% I) were susceptible to piperacillin-tazobactam. The mean age of the patients was 64 (±20) and they showed a 30-day mortality of 27%. The source of infection was in 65.3% of the cases abdominal, 20.4% were sacral pressure ulcers and 14.3% were unknown causes. While all isolates were fully susceptible at standard dosing regimen to amoxicillin-clavulanate, most were only susceptible at increased exposure or resistant to piperacillin-tazobactam. CONCLUSIONS: Our results suggest to be careful with the use of piperacillin-tazobactam and clindamycin in the empirical treatment of Eggerthella lenta infections.

Postpartum endometritis and obstetrical sepsis associated with Eggerthella lenta. Case report and review of the literature.

Sepsis, associated with Eggerthella lenta is rarely reported, despite current possibilities for microorganisms isolation and identification. About 100 cases of bacteriemia associated with this pathogen have been reported so far. Postpartum infectious complications are mostly associated with bacterial inhabitants of gastrointestinal tract and vagina, including obligatory anaerobes. This case report highlights E. lenta-associated severe endometritis complicated by abdominal sepsis in a young healthy woman, and the challenges of antibacterial therapy.

A rare case of an infected aortoiliac graft complicated with Eggerthella lenta bacteremia and septic shock.

We describe the successful medical management of an infected aorto-bi-Iliac endograft. In this case report, we provide an example of a patient with an infected aorto-bi-iliac endograft and how appropriate medical management may result in a positive outcome. We report a case of a 67-year-old man with several medical comorbidities who developed aorto-bi-iliac endograft infection one year after graft placement. The patient presented to our E.R. with fever, lethargy, tachycardia, tachypnea, and hypotension. The diagnosis of an infected endograft was established after excluding any other possible source of infection plus the strong radiological evidence by computed tomographic scan and WBCs labeled Indium-111 tropolone scan. Blood cultures revealed the development of Eggerthella lenta, Escherichia coli Extended-spectrum beta-lactamase (ESBL), and Enterococcus Faecalis. To our knowledge, this is a rare case of an infected endograft and bacteremia due to Eggerthella lenta. After the administration of vancomycin and Meropenem, no improvements were noted to the patient's clinical condition. However, upon the administration of Tigecycline, the patient's clinical condition improved. Two days later, repeat blood cultures were negative. After completion of the course of antibiotics and stabilization of other comorbidities, the patient was discharged home with long term antibiotic therapy under close control of inflammation markers.

Bacteremia Caused by the Eggerthella lenta in a Previously Healthy 30-Year-Old Man with Acute Suppurative Appendicitis: A Case Report from China.

Eggerthella lenta is part of the normal bacterial flora of the intestinal tract, but may cause life-threatening infections. E. lenta has been isolated from blood, abscesses, wounds, skin ulcers, and intra-abdominal infections. However, due to historical difficulties with laboratory identification by conventional biochemical methods, some cases of E. lenta infection have previously gone undiagnosed, especially in China where E. lenta infections are very rare. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), a new type of technology, has made it possible to identify E. lenta. We report a case of postoperative infection caused by E. lenta which was treated successfully using meropenem.

Eggerthella lenta bloodstream infections: two cases and review of the literature.

Eggerthella lenta is an emerging and uncommon human pathogen that has been under recognized due to the limitations of phenotypic identification. Here we describe two cases of bacteremia caused by E. lenta and summarize the results of antimicrobial susceptibility testing according to some previous literatures, which illustrate the importance of identification and treatment of unusual organisms. The most reliable antibiotic treatment options to E. lenta appear to be metronidazole, amoxicillin-clavulanate, carbapenems, vancomycin, cefoxitin, chloramphenicol and clindamycin.

The pharmaco-toxicological conundrum of oleander: Potential role of gut microbiome.

Nerium oleander L., commonly known as oleander, is a toxic shrub and also a medicinal plant. All parts of oleander are rich in cardiac glycosides that inhibits Na+/K+-ATPase and induce inotropic effect on the cardiomyocytes. Several pre-clinical and clinical reports indicate acute toxicity due to intentional, accidental and suicidal oleander consumption. Contrarily, oleander is used for the treatment of diverse ailments in traditional medicinal practices around the globe and several evidence-based pre-clinical studies indicated metabolic and immunological health benefits of polyphenol-rich oleander extracts. Thus, the current review aims to address this pharmaco-toxicological conundrum of oleander by addressing the possible role of gut microflora in the differential oleander toxicity. Additionally, a comprehensive account of ethnopharmacological usage, metabolic and immunological health benefits has been documented that supplement the conflicting arguments of pharmaco-toxicological properties of oleander. Finally, by addressing the gap of knowledge of ethnomedicinal, pharmacological and toxicological reports of oleander, the current review is expected to pave the way to address the differential pharmaco-toxicological effects of oleander.