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Estimation of silent phenotypes of calf antibiotic dysbiosis.

ABSTRACT: Reducing antibiotic usage among livestock animals to prevent antimicrobial resistance has become an urgent issue worldwide. This study evaluated the effects of administering chlortetracycline (CTC), a versatile antibacterial agent, on the performance, blood components, fecal microbiota, and organic acid concentrations of calves. Japanese Black calves were fed with milk replacers containing CTC at 10 g/kg (CON group) or 0 g/kg (EXP group). Growth performance was not affected by CTC administration. However, CTC administration altered the correlation between fecal organic acids and bacterial genera. Machine learning (ML) methods such as association analysis, linear discriminant analysis, and energy landscape analysis revealed that CTC administration affected populations of various types of fecal bacteria. Interestingly, the abundance of several methane-producing bacteria at 60 days of age was high in the CON group, and the abundance of Lachnospiraceae, a butyrate-producing bacterium, was high in the EXP group. Furthermore, statistical causal inference based on ML data estimated that CTC treatment affected the entire intestinal environment, potentially suppressing butyrate production, which may be attributed to methanogens in feces. Thus, these observations highlight the multiple harmful impacts of antibiotics on the intestinal health of calves and the potential production of greenhouse gases by calves.

SUBMITTER: Okada S

PROVIDER: S-EPMC10115819 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Estimation of silent phenotypes of calf antibiotic dysbiosis.

Okada Shunnosuke S Inabu Yudai Y Miyamoto Hirokuni H Suzuki Kenta K Kato Tamotsu T Kurotani Atsushi A Taguchi Yutaka Y Fujino Ryoichi R Shiotsuka Yuji Y Etoh Tetsuji T Tsuji Naoko N Matsuura Makiko M Tsuboi Arisa A Saito Akira A Masuya Hiroshi H Kikuchi Jun J Nagasawa Yuya Y Hirose Aya A Hayashi Tomohito T Ohno Hiroshi H Takahashi Hideyuki H

Scientific reports 20230419 1

Reducing antibiotic usage among livestock animals to prevent antimicrobial resistance has become an urgent issue worldwide. This study evaluated the effects of administering chlortetracycline (CTC), a versatile antibacterial agent, on the performance, blood components, fecal microbiota, and organic acid concentrations of calves. Japanese Black calves were fed with milk replacers containing CTC at 10 g/kg (CON group) or 0 g/kg (EXP group). Growth performance was not affected by CTC administration ...[more]

PMID: 37076584

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Project description:Health problems can be thought of as phenotypic expressions of the complex relationships between genes, environments, and phenomes as a whole. Detailed evaluations of phenotypic expressions of illness are required to characterize important biological outcomes. We hypothesized that classifying dairy calf mortality phenotypes via a systematic postmortem analysis would identify different cause-of-death diagnoses than those derived from treatments alone. This cross-sectional study was carried out on a dairy calf ranch in the northwestern United States from June to September 2017 and focused on calves ≤90 d of age. Comparisons were made between causes of death based on 3 levels of information: on-farm treatment records alone, necropsy-based postmortem analyses in addition to treatment records, and Washington Animal Disease Diagnostic Laboratory (WADDL) results in addition to all other information. A total of 210 dairy calves were necropsied during this study, of which 122 cases were submitted to WADDL. Necropsy- and WADDL-derived mortality phenotypes were in almost perfect agreement (Cohen's κ = 0.86) when broadly categorized as diarrhea, respiratory, diarrhea and respiratory combined, or other causes. The level of agreement between on-farm treatment records and postmortem-derived results was low and varied by the level of diagnostic detail provided. There was just fair agreement (κ = 0.22) between treatment-based and necropsy-based phenotypes without WADDL input and only slight agreement (κ = 0.13) between treatment-based and corresponding necropsy-based phenotypes with WADDL input. Even for those cases in which causes of death aligned along a comparable pathologic spectrum, the lack of detail inherent to standard treatment-based causes of death failed to identify meaningful target areas for intervention. This was especially apparent for numerous cases of necrotizing enteritis and typhlitis (cecal inflammation) that were variously categorized as diarrhea and pneumonia by treatment-based diagnoses. The specificity of these lesions stood in stark contrast to the otherwise generic cause of death diagnoses derived from treatments. The findings from this study supported the hypothesis and highlighted the value of on-farm necropsies and laboratory-based diagnostics to (1) detect antemortem disease misclassifications, (2) provide detail regarding disease processes and mortality phenotypes, and (3) direct disease mitigation strategies.

Project description:IntroductionThe gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics.MethodsFemale C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control). Caecal microbiota composition was assessed via 16S rRNA sequencing and caecal metabolites were quantified with NMR spectroscopy. Immune profiles of spleen and mesenteric lymph nodes (MLNs) were assessed by flow cytometry, and splenocytes assessed for ex vivo cytokine production. A generalised additive model approach was used to examine the relationship between global antibiotic consumption and IBD incidence.ResultsAntibiotics significantly altered gut microbiota composition, reducing alpha-diversity. Acetate and butyrate were significantly reduced in antibiotic groups, while propionate and succinate increased in Vancomycin and PmB-treated mice, respectively. The MLNs and spleen showed changes only to DC numbers. Splenocytes from antibiotic-treated mice stimulated ex vivo exhibited increased production of TNF. Epidemiological analysis revealed a positive correlation between global antibiotic consumption and IBD incidence.DiscussionOur findings demonstrate that antibiotic-mediated dysbiosis results in significantly altered short-chain fatty acid levels but immune homeostasis in spleen and MLNs at steady state is mostly preserved. Non-specific activation of splenocytes ex vivo, however, revealed mice with perturbed microbiota had significantly elevated production of TNF. Thus, this highlights antibiotic-mediated disruption of the gut microbiota may program the host towards dysregulated immune responses, predisposing to the development of TNF-associated autoimmune or chronic inflammatory disease.

Project description:Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations.IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain background on resistance phenotypes. Combinations of several different mutations showed a large amount of phenotypic predictability, and the majority of the mutations displayed strain-independent phenotypes. However, we also identified a few outliers from these patterns, illustrating that the choice of host organism can be critically important when studying antibiotic resistance mutations.

Dataset Information

Estimation of silent phenotypes of calf antibiotic dysbiosis.

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Estimation of silent phenotypes of calf antibiotic dysbiosis.

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