Metabolomic profiles in healthy research cats receiving clindamycin with a synbiotic or a placebo: a randomized, controlled trial (Part II)
Ontology highlight
ABSTRACT:
ORGANISM(S): Felis Catus
TISSUE(S): Feces
DISEASE(S): Antibiotic Resistance
PROVIDER: ST000981 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination. Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5-7 (baseline), 26-28, and 82-84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg's False Discovery Rate used to adjust for multiple comparisons. Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82-84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82-84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis) [Ruminococcus], Erysipelotrichaceae_g_, [Eubacterium], and Succinivibrionaceae_g_. Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae_g_, and Prevotella. Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82-84. Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics.
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Project description:Reduction in antibiotic-associated gastrointestinal signs (AAGS) in people co-administered probiotics is believed to result from shifts in the microbiome and metabolome. Amelioration of AAGS in cats secondary to synbiotic administration has recently been demonstrated. Thus, the aim of this randomized, double-blinded, placebo-controlled trial was to characterize associated changes in the fecal microbiome and metabolome. Sixteen healthy research cats received clindamycin with food, followed 1 h later by either a placebo or synbiotic, daily for 21 days. Fecal samples were collected during baseline, antibiotic administration, and 6 weeks after antibiotic discontinuation. Sequencing of 16S rRNA genes was performed, and mass spectrometry was used to determine fecal metabolomic profiles. Results were compared using mixed-model analyses, with P < 0.05 considered significant. Alpha and beta diversity were altered significantly during treatment, with persistent changes in the Shannon and dysbiosis indices. The relative abundance of Actinobacteria (Adlercreutzia, Bifidobacterium, Collinsella, Slackia), Bacteroidia (Bacteroides, Prevotella), Ruminococcaceae (Faecalibacterium, Ruminococcus), Veillonellaceae (Megamonas, Megasphaera, Phascolarctobacterium) and Erysipelotrichaceae ([Eubacterium]) decreased and relative abundance of Clostridiaceae (Clostridium) and Proteobacteria (Enterobacteriaceae) increased during treatment, followed by variable return to baseline relative abundances. Derangements in short-chain fatty acid (SCFA), bile acid, tryptophan, sphingolipid, polyamine, benzoic acid, and cinnaminic acid pathways occurred with significant group by time, group, and time interactions for 10, 5, and 106 metabolites, respectively. Of particular note were changes related to polyamine synthesis. Further investigation is warranted to elucidate the role of these alterations in prevention of AAGS in cats, people, and other animals treated with synbiotics.
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Project description:BackgroundAntibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic.Methods16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (eight cats) or commercially-available synbiotic (eight cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last three days of baseline (days 5-7), treatment (26-28), and recovery (631-633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P < 0.05 was considered significant. The Benjamini & Hochberg's False Discovery Rate was used to adjust for multiple comparisons.ResultsMedian age was six and five years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26-28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631-633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups.DiscussionCats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.
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Project description:Background & aimsPorto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD or cirrhosis to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways.MethodsSerum samples from 20 healthy volunteers (HVs), 20 patients with histologically confirmed PSVD or 20 patients with cirrhosis were analyzed. Metabolites were measured using liquid chromatography-mass spectrometry. Differential abundance was evaluated with Limma's moderated t-statistics. Artificial neural network and support vector machine models were developed to classify PSVD against cirrhosis or HV metabolomic profiles. An independent cohort was used for validation.ResultsA total of 283 metabolites were included for downstream analysis. Clustering effectively separated PSVD from HV metabolomes, although a subset of patients with PSVD (n = 5, 25%) overlapped with those with cirrhosis. Differential testing revealed significant PSVD-linked metabolic perturbations, including pertubations in taurocholic and adipic acids, distinguishing patients with PSVD from both HVs and those with cirrhosis. Alterations in pyrimidine, glycine, serine, and threonine pathways were exclusively associated with PSVD. Machine learning models utilizing selected metabolic signatures reliably differentiated the PSVD group from HVs or patients with cirrhosis using only 4 to 6 metabolites. Validation in an independent cohort demonstrated the high discriminative ability of taurocholic acid (AUROC 0.899) for patients with PSVD vs. HVs and the taurocholic acid/aspartic acid ratio (AUROC 0.720) for PSVD vs. cirrhosis.ConclusionsHigh-throughput metabolomics enabled the identification of distinct metabolic profiles that differentiate between PSVD, cirrhosis, and healthy individuals. Unique alterations in the glycine, serine, and threonine pathways suggest their potential involvement in PSVD pathogenesis.Impact and implicationsPorto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in patients with PSVD, including alterations in the pyrimidine, glycine, serine and threonine pathways, potentially shedding light on the disease's underlying pathways. These findings could enable earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.
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Project description:We report for the first time movement of Correia Repeat Enclosed Elements, through inversion of the element at its chromosomal location. Analysis of Ion Torrent generated genome sequence data from Neisseria gonorrhoeae strain NCCP11945 passaged for 8 weeks in the laboratory under standard conditions and stress conditions revealed a total of 37 inversions: 24 were exclusively seen in the stressed sample; 7 in the control sample; and the remaining 3 were seen in both samples. These inversions have the capability to alter gene expression in N. gonorrhoeae through the previously determined activities of the sequence features of these elements. In addition, the locations of predicted non-coding RNAs were investigated to identify potential associations with CREE. Associations varied between strains, as did the number of each element identified. The analysis indicates a role for CREE in disrupting ancestral regulatory networks, including non-coding RNAs. RNA-Seq was used to examine expression changes related to Correia repeats in the strain
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