Clostridium sporogenes increases fat accumulation in mice by enhancing energy absorption and adipogenesis.

Gut bacteria belonging to the Clostridium family play a pivotal role in regulating host energy balance and metabolic homeostasis. As a commensal bacterium, Clostridium sporogenes has been implicated in modulating host energy homeostasis, albeit the underlying mechanism remains elusive. Therefore, this study aimed to investigate the impact of C. sporogenes supplementation on various physiological parameters, intestinal morphology, particularly adipose tissue accumulation, and glucolipid metabolism in mice. The findings reveal that mice supplemented with C. sporogenes for 6 weeks exhibited a notable increase in body weight, fat mass, adipocyte size, and serum triglyceride (TG) levels. Notably, the increased fat accumulation is observed despite consistent feed intake in treated mice. Mechanistically, C. sporogenes supplementation significantly improved the structure integrity of intestinal villi and enhanced energy absorption efficiency while reducing excretion of carbohydrates and fatty acids in feces. This was accompanied by upregulation of glucose and fatty acid transporter expression. Furthermore, supplementation with C. sporogenes promoted adipogenesis in both liver and adipose tissues, as evidenced by increased levels of hepatic pyruvate, acetyl-CoA, and TG, along with elevated expression levels of genes associated with lipid synthesis. Regarding the microbiological aspect, C. sporogenes supplementation correlated with an increased abundance of Clostridium genus bacteria and enhanced carbohydrate enzyme activity. In summary, C. sporogenes supplementation significantly promotes fat accumulation in mice by augmenting energy absorption and adipogenesis, possibly mediated by the expansion of Clostridium bacteria population with robust glycolipid metabolic ability. IMPORTANCE: The Clostridia clusters have been implicated in energy metabolism, the specific species and underlying mechanisms remain unclear. This present study is the first to report Clostridium sporogenes is able to affect fat accumulation and glycolipid metabolism. We indicated that gavage of C. sporogenes promoted the adipogenesis and fat accumulation in mice by not only increasing the abundance of Clostridium bacteria but by also enhancing the metabolic absorption of carbohydrates and fatty acids significantly. Obviously, changes of gut microbiota caused by the C. sporogenes, especially the significant increase of Clostridium bacteria, contributed to the fat accumulation of mice. In addition, the enhancement of Clostridium genus bacteria remarkably improved the synthesis of hepatic pyruvate, acetyl-CoA, and triglyceride levels, as well as reduced the excretion of fecal carbohydrates, short-chain fatty acids, and free fatty acids remarkably. These findings will help us to understand the relationship of specific bacteria and host energy homeostasis.

SpoIVA is an essential morphogenetic protein for the formation of heat- and lysozyme-resistant spores in Clostridium sporogenes NBRC 14293.

Clostridium sporogenes is an anaerobic spore-forming bacterium genetically related to Clostridium botulinum but lacks toxin genes. The sporulation mechanism and spore structures of anaerobic bacteria, including C. sporogenes, have not been comprehensively analyzed. Based on 16S rRNA gene analysis, it has been determined that C. sporogenes NBRC 14293 belongs to C. botulinum Group I. Moreover, SpoIVA is highly conserved in Bacillus and Clostridium species. Therefore, the aim of the present study is to investigate the mechanism of spore formation in C. sporogenes by performing a functional analysis of spoIVA encoding SpoIVA, a protein involved in the early development of the spore coat and cortex in Bacillus subtilis. Inactivation of spoIVA in C. sporogenes resulted in the loss of resistance of sporulating cells to lysozyme and heat treatments. Phase-contrast microscopy indicated that the inactivation of spoIVA caused the development of abnormal forespores and production of only a few immature spores. In the spoIVA mutant, abnormal swirl structures were detected in the mother cell using both phase-contrast and transmission electron microscopy. These swirls were stained with auramine O, pararosaniline hydrochloride, and 2-(4-aminophenyl)benzothiazole to examine the surface of mature spores of the wild-type strain. We found that the spore coat and exosporium proteins were misassembled and that they accumulated in the mother cells of the mutant. The results of this study indicate that SpoIVA is a spore morphogenetic protein, providing novel insights into spore morphogenesis in C. sporogenes.

Antimicrobial effects of cannabidiol on select agriculturally important Clostridia.

Amino acid-fermenting Clostridia have undesirable effects in agricultural systems, which can be mitigated by antibiotics, but resistance necessitates alternatives. Here, we demonstrate the efficacy of cannabidiol on growth and ammonia inhibition of five agriculturally relevant Clostridia: Clostridium sporogenes, Peptostreptococcus spp., Clostridioides difficile, Acetoanaerobium sticklandii, and Clostridium aminophilum.

Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor.

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. A dramatic decrease in estrogen levels in postmenopausal women leads to osteoclast overactivation, impaired bone homeostasis, and subsequent bone loss. Changes in the gut microbiome affect bone mineral density. However, the role of the gut microbiome in estrogen deficiency-induced bone loss and its underlying mechanism remain unknown. In this study, we found that the abundance of Clostridium sporogenes (C. spor.) and its derived metabolite, indole propionic acid (IPA), were decreased in ovariectomized (OVX) mice. In vitro assays suggested that IPA suppressed osteoclast differentiation and function. At the molecular level, IPA suppressed receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced pregnane X receptor (PXR) ubiquitination and degradation, leading to increased binding of remaining PXR with P65. In vivo daily IPA administration or repeated C. spor. colonization protected against OVX-induced bone loss. To protect live bacteria from the harsh gastric environment and delay the emptying of orally administered C. spor. from the intestine, a C. spor.-encapsulated silk fibroin (SF) hydrogel system was developed, which achieved bone protection in OVX mice comparable to that achieved with repeated germ transplantation or daily IPA administration. Overall, we found that gut C. spor.-derived IPA was involved in estrogen deficiency-induced osteoclast overactivation by regulating the PXR/P65 complex. The C. spor.-encapsulated SF hydrogel system is a promising tool for combating postmenopausal osteoporosis without the disadvantages of repeated germ transplantation.

Cracking spoilage in jar cream cheese: Introducing, modeling and preventing.

This study aimed to investigate the modeling of antimicrobial activity (AA) of nisin and sorbate on Clostridium sporogenes in jar cream cheese (JCC) using the linear regression (LR), multilayer perceptron (MLP) neural network, and reduced error pruning tree (REPTree) methods, in order to prevent the late blowing defect (LBD) in the cheese. Both preservatives used in JCC samples showed AA against C. sporogenes; so that sorbate at all the concentrations used in JCC samples inhibited cracking spoilage during storage period at 35 °C. However, nisin could not inhibit cracking spoilage at concentration of 30 ppm in the samples, and a higher concentration of it was needed. The three models used in this study, followed the similar pattern in both training and validation datasets for nisin and sorbat in JCC. The R2 and root mean square error (RMSE) values of training and validation datasets showed the superiority of the REPTree model compared to the MLP and LR models (conventional methods) in the modeling of AA of nisin and sorbate against C. sporogenes in JCC.

Modeling interactions of Clostridium cadaveris and Clostridium sporogenes in anaerobic acidogenesis of glucose and peptone.

This study focuses on developing a mathematical model to assess interaction among acidogenic bacteria during the anaerobic degradation of two substrates. Clostridium cadaveris and Clostridium sporogenes were cultured in various combinations with glucose and peptone. Parameter estimates are given for both conventional Monod parameters from single substrate-single species cultures and sum kinetics with interaction parameters obtained from dual substrate-single species cultures. The presence of multiple substrates led to both inhibitory and enhancing effects on biodegradation rates for dual substrates compared to single substrate cultures. A new model of interspecies interaction was developed within the framework of Lotka-Volterra incorporating substrate interaction parameters, with a focus on accuracy, realism, simplicity, and biological significance. The model demonstrated competitive interaction for resource sharing and the additional non-linearity parameter eliminated the constraint of the linear relationship between growth rate and population density.

Refined control of CRISPR-Cas9 gene editing in Clostridium sporogenes: the creation of recombinant strains for therapeutic applications.

Despite considerable clinical success, the potential of cancer immunotherapy is restricted by a lack of tumour-targeting strategies. Treatment requires systemic delivery of cytokines or antibodies at high levels to achieve clinically effective doses at malignant sites. This is exacerbated by poor penetration of tumour tissue by therapeutic antibodies. High-grade immune-related adverse events (irAEs) occur in a significant number of patients (5-15%, cancer- and therapeutic-dependent) that can lead to lifelong issues and can exclude from treatment patients with pre-existing autoimmune diseases. Tumour-homing bacteria, genetically engineered to produce therapeutics, is one of the approaches that seeks to mitigate these drawbacks. The ability of Clostridium sporogenes to form spores that are unable to germinate in the presence of oxygen (typical of healthy tissue) offers a unique advantage over other vectors. However, the limited utility of existing gene editing tools hinders the development of therapeutic strains. To overcome the limitations of previous systems, expression of the Cas9 protein and the gRNA was controlled using tetracycline inducible promoters. Furthermore, the components of the system were divided across two plasmids, improving the efficiency of cloning and conjugation. Genome integrated therapeutic genes were assayed biochemically and in cell-based functional assays. The potency of these strains was further improved through rationally-conceived gene knock-outs. The new system was validated by demonstrating the efficient addition and deletion of large sequences from the genome. This included the creation of recombinant strains expressing two pro-inflammatory cytokines, interleukin-2 (IL-2) and granulocyte macrophage-colony stimulating factor (GM-CSF), and a pro-drug converting enzyme (PCE). A comparative, temporal in vitro analysis of the integrant strains and their plasmid-based equivalents revealed a substantial reduction of cytokine activity in chromosome-based constructs. To compensate for this loss, a 7.6 kb operon of proteolytic genes was deleted from the genome. The resultant knock-out strains showed an 8- to 10-fold increase in cytokine activity compared to parental strains.

Fatal Clostridium sporogenes Soft Tissue Polymicrobial Infections in Two Immunocompetent Cases: Case Report.

BACKGROUND: Clostridium sporogenes is reported rarely in literature. Reports from the skin and soft tissue infections are even less, more so in immunocompetent patients. CASE PRESENTATION: Two skin and soft tissue infections with C. sporogenes in immunocompetent patients have been presented in this study. One of the cases was following an electrical burn wound, and the other was following a bedsore. Both patients expired despite antibacterial treatment and debridement. DISCUSSION AND CONCLUSION: C. sporogenes had usually been reported after trauma particularly after penetrating and deep wound infection. More attention should be given to these patients so that the infection can be treated and diagnosed early in suspected anaerobic infections like Clostridium species.

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.

Tryptophan was metabolized into beneficial metabolites against coronary heart disease or prevented from producing harmful metabolites by the in vitro drug screening model based on Clostridium sporogenes.

In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography-mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota.

Polyphenolic Characterization, Antioxidant, Antihyaluronidase and Antimicrobial Activity of Young Leaves and Stem Extracts from Rubus caesius L.

Fruits are the main food part of the European dewberry (Rubus caesius L.), known as a source of polyphenols and antioxidants, while very little attention is paid to leaves and stems, especially young first-year stems. The purpose of this work was to analyze for the first time water and ethanol extracts obtained from young, freshly developed, leaves and stems of the European dewberry to determine their antioxidant and biological activity, whereas most of the papers describe biological properties of leaves collected during summer or autumn. As the phytochemical profile changes during the growing season, the quantitative and qualitative content of flavonoid glycosides and flavonoid aglycones was analyzed using reversed phase liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (LC-ESI-MS/MS) with multiple reaction monitoring (MRM). The ability to inhibit hyaluronidase as well as antioxidant activity (2,2 diphenyl-1-picrylhydrazyl: DPPH and ferric antioxidant power: FRAP) were estimated. Extracts were also analyzed against Gram-positive and Gram-negative bacteria. The results of the qualitative phytochemical analysis indicated the presence of flavonoid aglycones and flavonoid glycosides, with the highest amount of tiliroside, hyperoside, isoquercetin, astragalin, rutin and catechin in ethanol extracts. DPPH and FRAP tests proved the high antioxidant activity of the extracts from leaves or stems and the antihyaluronidase assay revealed for the first time that water and ethanol extracts obtained from the stems exhibited the ability to inhibit hyaluronidase activity resulting in an IC50 of 55.24 ± 3.21 and 68.7 ± 1.61 µg/mL, respectively. The antimicrobial activity has never been analyzed for European dewberry and was the highest for Clostridium bifermentans and Clostridium sporogenes-anaerobic sporulation rods as well as Enterococcus faecalis for both water and ethanol extracts.

Susceptibility of Clostridium sporogenes Spores to Selected Reference Substances and Disinfectants.

Research on the susceptibility of the spores of anaerobic bacteria such as Clostridium sporogenes or Clostridioides difficile is vital for assessing the sporicidal activity of disinfectants. The diverse susceptibility of anaerobic bacteria spores may lead to different disinfection parameters being determined by laboratories that prepare spore suspensions to test sporicidal effectiveness. The tests were performed using the suspension method according to PN-EN 13704:2018-09. In order to assess the susceptibility of the C. sporogenes spores, the criterion established for the C. difficile ribotype 027 spores was used in accordance with PN­EN 17126:2019-01. The susceptibility of the C. sporogenes spores to glutardialdehyde corresponded to the susceptibility ranges established for the C. difficile ribotype 027 spores. The C. sporogenes spore suspension was susceptible to low concentrations of peracetic acid (0.01%). A disinfectant containing peracetic acid as the active substance showed high sporicidal activity at a low concentration (1%), a short contact time (15 minutes), and a high organic load (3.0 g/l bovine albumin + 3.0 ml/l sheep erythrocytes), as compared to a disinfectant with glutardialdehyde, which was sporicidal at a higher concentration (2.5%), at a longer contact time (60 minutes) and lower organic conditions (3.0 g/l bovine albumin). There is a need to define the minimum susceptibility criteria for the C. sporogenes spores to the reference substances most often found in disinfectants with sporicidal activity. Excessive susceptibility of the C. sporogenes spores to reference substances may result in low-performance parameters of disinfection products with sporicidal activity and lead to ineffective disinfection in practice.

Isolation, Characterization, and Application of Clostridium sporogenes F39 to Degrade Zearalenone under Anaerobic Conditions.

Zearalenone (ZEN) is produced by Fusarium spp. and is widely found in moldy wheat, corn, and other grains. ZEN has a strong toxicity and causes reproductive and immune disorders and estrogenic syndrome in animals and humans. Biodegradation has been demonstrated as an efficient way to control the hazardous effect of ZEN. A promising way to apply biodegradation in feed is to introduce anaerobic ZEN-degrading microorganisms, which can function during the digestion process in animal intestines. The aim of this study was to isolate anaerobic ZEN-degrading bacteria from anaerobic environments. A strain named F39 was isolated from animal intestinal contents and had a ZEN-degradation rate of 87.35% in 48 h to form trace amount of α- and ß-zearalenol. Based on the morphological and physiological properties and phylogenetic analysis of 16S rRNA and rpoB gene sequences, F39 was identified as Clostridium sporogenes. The optimum temperature for the growth of F39 was 37 °C, the optimum pH was 7.0, and the most suitable carbon source was beef extract, while the optimal conditions for the degradation of ZEN were as follows: 35 °C, pH 7.0, and GAM medium. ZEN was degraded by F39 with a high efficiency in the concentration range of 1-15 mg/L. The bioactive factors responsible for ZEN degradation were mainly distributed intracellularly. F39 can degrade most of the ZEN present, but a small amount is broken down into two secondary metabolites, α- and ß-zearalenol, and the toxicity of the degradation products is reduced. With an efficiency of 49%, F39 can more effectively degrade ZEN in wheat-based feedstuffs than in other feedstuff, and the degradation efficiency was pH related. To the best of our knowledge, this is the first report of Clostridium sporogenes F39's ability to maintain the biodegradation potentials.

Membrane Vesicles Derived From Clostridium botulinum and Related Clostridial Species Induce Innate Immune Responses via MyD88/TRIF Signaling in vitro.

Clostridium botulinum produces botulinum neurotoxin complexes that cause botulism. Previous studies elucidated the molecular pathogenesis of botulinum neurotoxin complexes; however, it currently remains unclear whether other components of the bacterium affect host cells. Recent studies provided insights into the role of bacterial membrane vesicles (MVs) produced by some bacterial species in host immunity and pathology. We herein examined and compared the cellular effects of MVs isolated from four strains of C. botulinum with those of closely related Clostridium sporogenes and two strains of the symbiont Clostridium scindens. MVs derived from all strains induced inflammatory cytokine expression in intestinal epithelial and macrophage cell lines. Cytokine expression was dependent on myeloid differentiation primary response (MyD) 88 and TIR-domain-containing adapter-inducing interferon-ß (TRIF), essential adaptors for toll-like receptors (TLRs), and TLR1/2/4. The inhibition of actin polymerization impeded the uptake of MVs in RAW264.7 cells, however, did not reduce the induction of cytokine expression. On the other hand, the inhibition of dynamin or phosphatidylinositol-3 kinase (PI3K) suppressed the induction of cytokine expression by MVs, suggesting the importance of these factors downstream of TLR signaling. MVs also induced expression of Reg3 family antimicrobial peptides via MyD88/TRIF signaling in primary cultured mouse small intestinal epithelial cells (IECs). The present results indicate that MVs from C. botulinum and related clostridial species induce host innate immune responses.

Potential Risk of Botulinum Neurotoxin -producing Clostridia Occurrence in Canned Fish.

Introduction: Heat treatment is indispensable in fish canning to provide an acceptable shelf life. Its optimisation reduces the risk of the presence of Clostridium botulinum spores, which could potentially cause botulism cases. This study evaluated canned fish samples for botulism neurotoxin (BoNT)-producing clostridia contamination and can bulging through microbiological contaminant growth. A new analytical approach was developed for detection of such clostridia and phenotypically similar species. Material and Methods: A total of 70 canned fish samples suspected of exhibiting bulging features were analysed. Culture methods were used to detect clostridia. The isolates obtained were evaluated on the basis of the exhibited phenotypic characteristics. Also, PCRs were used for the detection of genes determining BoNT production (non-toxic non-haemagglutinin (ntnh) genes) and the amplification of conservative 16S rDNA genes, which were Sanger sequenced. The obtained sequences were analysed using the Basic Local Alignment Search Tool. Results: Clostridium genus species were isolated from 17 (24%) bulging and organoleptically changed samples. No ntnh genes were present in these isolates; however, sequencing confirmed the presence of C. sporogenes, a species with close affinity to C. botulinum. Conclusion: To eliminate the threat of foodborne botulism, laboratory diagnostic techniques must detect species of the Clostridium genus and elucidate their ability to produce BoNTs. Although Clostridium botulinum is the most common cause of botulism, the possibility may not be ignored that non-pathogenic Clostridium species may acquire botulinum toxigenicity. The similarity between the isolated strains of C. sporogenes and C. botulinum should be incorporated in the optimisation of heat treatment to guarantee a sterilised, microbiologically safe product.

Investigation of the Effectiveness of Disinfectants Used in Meat-Processing Facilities to Control Clostridium sporogenes and Clostridioides difficile Spores.

Spore-forming bacteria are a major concern for the food industry as they cause both spoilage and food safety issues. Moreover, as they are more resistant than vegetative cells, their removal from the food processing environment may be difficult to achieve. This study investigated the efficacy of the ten most commonly used disinfectant agents (assigned 1-10), used at the recommended concentrations in the meat industry, for their ability to eliminate Clostridium sporogenes and Clostridioides difficile spores. Test-tube based suspension assays suggested that disinfectants 2 (10% v/v preparation of a mixture of hydrogen peroxide (10-30%), acetic acid (1-10%) and peracetic acid (1-10%)), 7 (4% w/v preparation of a mixture of peroxymonosulphate (30-50%), sulphamic acid (1-10%) and troclosene sodium (1-10%)) and 10 (2% v/v preparation of a mixture of glutaraldehyde (10-30%), benzalkonium chloride (1-10%)) were the most effective formulations. D-values for these ranged from 2.1 to 8.4 min at 20 °C for the target spores. Based on these findings, it is recommended that these disinfectants are used to control Clostridium spores in the meat plant environment.

Clostridium botulinum - like organism bacteremia in a user of black tar heroin.

Wound botulism due to introduction of the anaerobic bacteria, Clostridium botulinum, into otherwise sterile, relatively anaerobic tissue is a known complication of black tar heroin use. The treatment of wound botulism requires prompt initiation of antitoxin as well as antimicrobial therapy. We report the case of a patient with polymicrobial bacteremia that included a Clostridium botulinum-like organism who underwent successful treatment of their anaerobic infection with antibiotics and surgical debridement.

Endogenous CRISPR-Cas Systems in Group I Clostridium botulinum and Clostridium sporogenes Do Not Directly Target the Botulinum Neurotoxin Gene Cluster.

Most strains of proteolytic group I Clostridium botulinum (G1 C. botulinum) and some strains of Clostridium sporogenes possess genes encoding botulinum neurotoxin (BoNT), a potent neuroparalytic agent. Within G1 C. botulinum, conserved bont gene clusters of three major toxin serotypes (bont/A/B/F) can be found on conjugative plasmids and/or within chromosomal pathogenicity islands. CRISPR-Cas systems enable site-specific targeting of previously encountered mobile genetic elements (MGE) such as plasmids and bacteriophage through the creation of a spacer library complementary to protospacers within the MGEs. To examine whether endogenous CRISPR-Cas systems restrict the transfer of bont gene clusters across strains we conducted a bioinformatic analysis profiling endogenous CRISPR-Cas systems from 241 G1 C. botulinum and C. sporogenes strains. Approximately 6,200 CRISPR spacers were identified across the strains and Type I-B, III-A/B/D cas genes and CRISPR array features were identified in 83% of the strains. Mapping the predicted spacers against the masked strain and RefSeq plasmid dataset identified 56,000 spacer-protospacer matches. While spacers mapped heavily to targets within bont(+) plasmids, no protospacers were identified within the bont gene clusters. These results indicate the toxin is not a direct target of CRISPR-Cas but the plasmids predominantly responsible for its mobilization are. Finally, while the presence of a CRISPR-Cas system did not reliably indicate the presence or absence of a bont gene cluster, comparative genomics across strains indicates they often occupy the same hypervariable loci common to both species, potentially suggesting similar mechanisms are involved in the acquisition and curation of both genomic features.

Gut bacterial deamination of residual levodopa medication for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Gastrointestinal tract dysfunction is one of the non-motor features, where constipation is reported as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and host's physiology. In particular, Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut. RESULTS: Here, we show that C. sporogenes deaminates levodopa, the main treatment in Parkinson's disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in an ex vivo model. We detected 3-(3,4-dihydroxyphenyl)propionic acid in fecal samples of Parkinson's disease patients on levodopa medication and found that this metabolite is actively produced by the gut microbiota in those stool samples. CONCLUSIONS: Levodopa is deaminated by the gut bacterium C. sporogenes producing a metabolite that inhibits ileal motility ex vivo. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.