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The Serum and Fecal Metabolomic Profiles of Growing Kittens Treated with Amoxicillin/Clavulanic Acid or Doxycycline.

ABSTRACT: The long-term impact of antibiotics on the serum and fecal metabolome of kittens has not yet been investigated. Therefore, the objective of this study was to evaluate the serum and fecal metabolome of kittens with an upper respiratory tract infection (URTI) before, during, and after antibiotic treatment and compare it with that of healthy control cats. Thirty 2-month-old cats with a URTI were randomly assigned to receive either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days, and 15 cats of similar age were enrolled as controls. Fecal samples were collected on days 0, 20/28, 60, 120, and 300, while serum was collected on days 0, 20/28, and 300. Untargeted and targeted metabolomic analyses were performed on both serum and fecal samples. Seven metabolites differed significantly in antibiotic-treated cats compared to controls on day 20/28, with two differing on day 60, and two on day 120. Alterations in the pattern of serum amino acids, antioxidants, purines, and pyrimidines, as well as fecal bile acids, sterols, and fatty acids, were observed in antibiotic-treated groups that were not observed in control cats. However, the alterations caused by either amoxicillin/clavulanic acid or doxycycline of the fecal and serum metabolome were only temporary and were resolved by 10 months after their withdrawal.

SUBMITTER: Stavroulaki EM

PROVIDER: S-EPMC8833518 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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The Serum and Fecal Metabolomic Profiles of Growing Kittens Treated with Amoxicillin/Clavulanic Acid or Doxycycline.

Stavroulaki Evangelia M EM Suchodolski Jan S JS Pilla Rachel R Fosgate Geoffrey T GT Sung Chi-Hsuan CH Lidbury Jonathan J Steiner Jörg M JM Xenoulis Panagiotis G PG

Animals : an open access journal from MDPI 20220129 3

The long-term impact of antibiotics on the serum and fecal metabolome of kittens has not yet been investigated. Therefore, the objective of this study was to evaluate the serum and fecal metabolome of kittens with an upper respiratory tract infection (URTI) before, during, and after antibiotic treatment and compare it with that of healthy control cats. Thirty 2-month-old cats with a URTI were randomly assigned to receive either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days, ...[more]

PMID: 35158655

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Project description:Antibiotic treatment in early life influences gastrointestinal (GI) microbial composition and function. In humans, the resultant intestinal dysbiosis is associated with an increased risk for certain diseases later in life. The objective of this study was to determine the temporal effects of antibiotic treatment on the GI microbiome of young cats. Fecal samples were collected from cats randomly allocated to receive either amoxicillin/clavulanic acid (20 mg/kg q12h) for 20 days (AMC group; 15 cats) or doxycycline (10 mg/kg q24h) for 28 days (DOX group;15 cats) as part of the standard treatment of upper respiratory tract infection. In addition, feces were collected from healthy control cats (CON group;15 cats). All cats were approximately two months of age at enrolment. Samples were collected on days 0 (baseline), 20 or 28 (AMC and DOX, respectively; last day of treatment), 60, 120, and 300. DNA was extracted and sequencing of the 16S rRNA gene and qPCR assays were performed. Fecal microbial composition was different on the last day of treatment for AMC cats, and 1 month after the end of antibiotic treatment for DOX cats, compared to CON cats. Species richness was significantly greater in DOX cats compared to CON cats on the last day of treatment. Abundance of Enterobacteriales was increased, and that of Erysipelotrichi was decreased in cats of the AMC group on the last day of treatment compared to CON cats. The abundance of the phylum Proteobacteria was increased in cats of the DOX group on days 60 and 120 compared to cats of the CON group. Only minor differences in abundances between the treatment groups and the control group were present on day 300. Both antibiotics appear to delay the developmental progression of the microbiome, and this effect is more profound during treatment with amoxicillin/clavulanic acid and one month after treatment with doxycycline. Future studies are required to determine if these changes influence microbiome function and whether they have possible effects on disease susceptibility in cats.

Project description:Amoxicillin-clavulanic acid (AMC) is one of the most frequently prescribed antibiotic formulations in the Western world. Extensive oral use of this antimicrobial combination influences the gut microbiota. One of the most abundant early colonizers of the human gut microbiota is represented by different taxa of the Bifidobacterium genus, which include many members that are considered to bestow beneficial effects upon their host. In the current study, we investigated the impact of AMC administration on the gut microbiota composition, comparing the gut microbiota of 23 children that had undergone AMC antibiotic therapy to that of 19 children that had not been treated with antibiotics during the preceding 6 months. Moreover, we evaluated AMC sensitivity by MIC test of 261 bifidobacterial strains, including reference strains for the currently recognized 64 bifidobacterial (sub)species, as well as 197 bifidobacterial isolates of human origin. These assessments allowed the identification of four bifidobacterial strains that exhibit a high level of AMC insensitivity, which were subjected to genomic and transcriptomic analyses to identify the putative genetic determinants responsible for this AMC insensitivity. Furthermore, we investigated the ecological role of AMC-resistant bifidobacterial strains by in vitro batch cultures.IMPORTANCE Based on our results, we observed a drastic reduction in gut microbiota diversity of children treated with antibiotics, which also affected the abundance of Bifidobacterium, a bacterial genus commonly found in the infant gut. MIC experiments revealed that more than 98% of bifidobacterial strains tested were shown to be inhibited by the AMC antibiotic. Isolation of four insensitive strains and sequencing of their genomes revealed the identity of possible genes involved in AMC resistance mechanisms. Moreover, gut-simulating in vitro experiments revealed that one strain, i.e., Bifidobacterium breve PRL2020, is able to persist in the presence of a complex microbiota combined with AMC antibiotic.

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Project description:The incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profiling in both brain (n = 109) and matching serum samples (n = 566) to identify differentially expressed metabolites and metabolic pathways associated with neuropathology and cognitive performance and to identify individuals at high risk of developing cognitive impairment. The abundances of 6 metabolites, glycolithocholate (GLCA), petroselinic acid, linoleic acid, myristic acid, palmitic acid, palmitoleic acid and the deoxycholate/cholate (DCA/CA) ratio, along with the dysregulation scores of 3 metabolic pathways, primary bile acid biosynthesis, fatty acid biosynthesis, and biosynthesis of unsaturated fatty acids showed significant differences across both brain and serum diagnostic groups (P-value < 0.05). Significant associations were observed between the levels of differential metabolites/pathways and cognitive performance, neurofibrillary tangles, and neuritic plaque burden. Metabolites abundances and personalized metabolic pathways scores were used to derive machine learning models, respectively, that could be used to differentiate cognitively impaired persons from those without cognitive impairment (median area under the receiver operating characteristic curve (AUC) = 0.772 for the metabolite level model; median AUC = 0.731 for the pathway level model). Utilizing these two models on the entire baseline control group, we identified those who experienced cognitive decline in the later years (AUC = 0.804, sensitivity = 0.722, specificity = 0.749 for the metabolite level model; AUC = 0.778, sensitivity = 0.633, specificity = 0.825 for the pathway level model) and demonstrated their pre-AD onset prediction potentials. Our study provides a proof-of-concept that it is possible to discriminate antecedent cognitive impairment in older adults before the onset of overt clinical symptoms using metabolomics. Our findings, if validated in future studies, could enable the earlier detection and intervention of cognitive impairment that may halt its progression.

Dataset Information

The Serum and Fecal Metabolomic Profiles of Growing Kittens Treated with Amoxicillin/Clavulanic Acid or Doxycycline.

Publications

The Serum and Fecal Metabolomic Profiles of Growing Kittens Treated with Amoxicillin/Clavulanic Acid or Doxycycline.

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