Abstract
BackgroundEstablishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.ResultsSpecifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor–recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.ConclusionsOverall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves.1SZe_1Amjvg5rTHsSJMvRbVideo abstract
Highlights
Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection
The efficacy of FMT treatments was determined using the diarrheal score, physical appearance, and performance from enteropathogenic microbial analysis of feces collected from the recipient calves just before and 1 week after each FMT treatment
A classical method was employed in fecal tests to identify the causative enteropathogens: 70% (14/20) of recipients were diagnosed with infectious calf diarrhea (CD), as indicated by the presence of C. perfringens, C. parvum, rotavirus, and/or coccidia in multiple calves with diarrhea (Fig. 1d)
Summary
Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. Maximizing the effects of FMT as a treatment for CD remains a challenge because the donor or recipient may be selected inappropriately due to gut microbiota compositions varying even within healthy populations as a result of environmental factors, farm management, and calf age [3]. These obstacles may increase the lack of reproducibility or the risk of FMT failure when attempting to prevent CD. Clinical veterinarians face a huge challenge to provide correct CD diagnoses; misdiagnosis may promote the improper use of antibiotics and emergence of antibioticresistant bacteria [11, 12]
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