Faecal pharmacokinetics, microbiome, and bile acid changes in healthy subjects given intravenous followed by oral omadacycline; a Phase 1 clinical trial.

Background: There is an urgent need to develop new antimicrobials effective intravenously for Clostridioides difficile infection (CDI). Omadacycline is an aminomethylcycline tetracycline available orally and intravenously with potent in vitro activity against C. difficile and a low propensity to cause CDI.

Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study.

Background: Clostridioides difficile infection is a common health-care-associated and community-acquired disease with few antibiotic treatment options. We aimed to assess the safety, efficacy, pharmacokinetics, and associated microbiome changes of ibezapolstat, an antibiotic that inhibits the PolC-type DNA polymerase III α subunit C, versus vancomycin for the treatment of C difficile infection in adults.

Methods: This was a phase 2b, randomised, double-blind, active-controlled study conducted at 15 centres, primarily outpatient clinics and hospitals, in the USA.

Antibiofilm properties of 4-hydroxy-3-methyl-2-alkenylquinoline, a novel -derived alkaloid.

Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem.

Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin.

Unlabelled: Omadacycline, an aminomethylcycline tetracycline, has a low propensity to cause infection (CDI) in clinical trials. Omadacycline exhibited a reduced bactericidal effect compared with vancomycin on key microorganisms implicated in bile acid homeostasis and short-chain fatty acids (SCFAs), key components of CDI pathogenesis. The purpose of this study was to assess bile acid and SCFA changes in stool samples from healthy volunteers given omadacycline or vancomycin.

colonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an model.

Treatment with antibiotics is a major risk factor for infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to growth and competition between the microbiota and for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to infection in 12 different microbial communities cultivated from healthy individuals.

Phylogenetically diverse bacterial species produce histamine.

Histamine is an important biogenic amine known to impact a variety of patho-physiological processes ranging from allergic reactions, gut-mediated anti-inflammatory responses, and neurotransmitter activity. Histamine is found both endogenously within specialized host cells and exogenously in microbes. Exogenous histamine is produced through the decarboxylation of the amino acid L-histidine by bacterial-derived histidine decarboxylase enzymes.

Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune-mediated liver injury.

Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intrahepatic and extrahepatic bile ducts of unclear etiology. PSC is commonly (in 60%-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation.

Characterizing arginine, ornithine, and putrescine pathways in enteric pathobionts.

Arginine-ornithine metabolism plays a crucial role in bacterial homeostasis, as evidenced by numerous studies. However, the utilization of arginine and the downstream products of its metabolism remain undefined in various gut bacteria. To bridge this knowledge gap, we employed genomic screening to pinpoint relevant metabolic targets.

Liquid Chromatography-Tandem Mass Spectrometry-Based Therapeutic Monitoring of Plasma Atovaquone Concentrations in Pediatric Patients.

Atovaquone is an FDA-approved antiparasitic and antifungal therapeutic that is currently used as a prophylactic agent to prevent Pneumocystis carinii pneumonia (PCP) infections in acute myeloid leukemia (AML) patients after receiving hematopoietic stem cell transplantation (HSCT). Recent studies have shown that atovaquone has shown potential as an anticancer agent. The high variability in atovaquone bioavailability prompts the need for therapeutic drug monitoring, especially in pediatric patients.

Repurposing dried blood spot device technology to examine bile acid profiles in human dried fecal spot samples.

Dried blood spot (DBS) analysis has existed for >50 years, but application of this technique to fecal analysis remains limited. To address whether dried fecal spots (DFS) could be used to measure fecal bile acids, we collected feces from five subjects for each of the following cohorts: ) healthy individuals, ) individuals with diarrhea, and ) infected patients. Homogenized fecal extracts were loaded onto quantitative DBS (qDBS) devices, dried overnight, and shipped to the bioanalytical lab at ambient temperature.

A high-throughput protocol for measuring solution pH of bacterial cultures using UV-Vis absorption spectrophotometry.

We present a protocol for measuring the pH of cell-free bacterial-conditioned media based on changes in the ultraviolet-visible (UV-Vis) absorbance spectrum using the pH indicator dye litmus. This protocol includes detailed procedures for performing bacterial culturing, examining bacterial growth, collecting cell-free supernatant, litmus dye addition, and pH-based calibration curve preparations. This assay has been designed for flexible formatting that can accommodate both high-volume and low-volume sample sets.

Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes.

Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients.

Background: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.

Interrogation of the mammalian gut-brain axis using LC-MS/MS-based targeted metabolomics with in vitro bacterial and organoid cultures and in vivo gnotobiotic mouse models.

Interest in the communication between the gastrointestinal tract and central nervous system, known as the gut-brain axis, has prompted the development of quantitative analytical platforms to analyze microbe- and host-derived signals. This protocol enables investigations into connections between microbial colonization and intestinal and brain neurotransmitters and contains strategies for the comprehensive evaluation of metabolites in in vitro (organoids) and in vivo mouse model systems. Here we present an optimized workflow that includes procedures for preparing these gut-brain axis model systems: (stage 1) growth of microbes in defined media; (stage 2) microinjection of intestinal organoids; and (stage 3) generation of animal models including germ-free (no microbes), specific-pathogen-free (complete gut microbiota) and specific-pathogen-free re-conventionalized (germ-free mice associated with a complete gut microbiota from a specific-pathogen-free mouse), and Bifidobacterium dentium and Bacteroides ovatus mono-associated mice (germ-free mice colonized with a single gut microbe).

Serum 3-phenyllactic acid level is reduced in benign multiple sclerosis and is associated with effector B cell ratios.

Background: 3-phenyllactic acid (PLA) is produced by both intestinal bacteria and the human host. PLA exists in its D- and L- chiral forms. It modulates human immune functions, thereby acting as a mediator of bacterial-host interactions.

Insights into Microbiome and Metabolic Signatures of Children Undergoing Peanut Oral Immunotherapy.

Background: Peanut oral immunotherapy has emerged as a novel, active management approach for peanut-allergic sufferers, but limited data exist currently on the role of the microbiome in successful desensitization.

Objective: We examined the oral and gut microbiome in a cohort of 17 children undergoing peanut oral immunotherapy with the aim to identify the microbiome signatures associated with successful desensitization. We also set out to characterize their fecal metabolic profiles after successful therapy.

Mathematical models to study the biology of pathogens and the infectious diseases they cause.

Mathematical models have many applications in infectious diseases: epidemiologists use them to forecast outbreaks and design containment strategies; systems biologists use them to study complex processes sustaining pathogens, from the metabolic networks empowering microbial cells to ecological networks in the microbiome that protects its host. Here, we (1) review important models relevant to infectious diseases, (2) draw parallels among models ranging widely in scale. We end by discussing a minimal set of information for a model to promote its use by others and to enable predictions that help us better fight pathogens and the diseases they cause.

Unraveling the Metabolic Requirements of the Gut Commensal .

Bacteroidetes are the most common bacterial phylum in the mammalian intestine and the effects of several spp. on multiple facets of host physiology have been previously described. Of the spp.

Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with .

Background: Accumulating evidence indicates that the gut microbiota can synthesize neurotransmitters as well as impact host-derived neurotransmitter levels. In the past, it has been challenging to decipher which microbes influence neurotransmitters due to the complexity of the gut microbiota.

Methods: To address whether a single microbe, could regulate important neurotransmitters, we examined genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS.

The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal.

Background: Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium.

Results: B.

-derived y-glutamylcysteine suppresses ER-mediated goblet cell stress and reduces TNBS-driven colonic inflammation.

Endoplasmic reticulum (ER) stress compromises the secretion of MUC2 from goblet cells and has been linked with inflammatory bowel disease (IBD). Although can beneficially modulate mucin production, little work has been done investigating the effects of on goblet cell ER stress. We hypothesized that secreted factors from downregulate ER stress genes and modulates the unfolded protein response (UPR) to promote MUC2 secretion.