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Evidence synthesis of probiotic supplementation to dairy calves and its safety: scoping review, meta-analysis, and antimicrobial resistance

Abstract

Probiotics, also known as direct-fed microbials, have been proposed as a strategy to improve growth and enhance health of dairy calves. However, the available literature regarding the efficacy of probiotic supplementation on calf growth and feed intake is inconsistent. Moreover, scarce information exists on the safety of commercially available cattle probiotics, particularly concerning their antibiotic resistance profile. Thus, the objectives of this dissertation were to: (i) identify, describe, and characterize the literature on probiotic supplementation in dairy calves, (ii) quantify the effect of probiotic supplementation, considering different probiotics combined and categorized by probiotic genus, on ADG, feed intake, and feed efficiency of dairy calves and (iii) evaluate the phenotypic antimicrobial susceptibility of Enterococcus and Bacillus ssp. isolated from commercially available cattle probiotics. For the first objective, a comprehensive scoping review was performed, compromising studies with non-randomized, quasi- randomized, and randomized controlled trials in English, Spanish, or Portuguese that evaluated the effect of probiotic supplementation on the growth and health of dairy calves. Searches were conducted in Biosis, CAB Abstracts, Medline, Scopus, and the Dissertations and Theses Database. In total, 4,467 records were retrieved, of which 103 studies (110 controlled trials) met the inclusion criteria. The studies were published between 1980 and 2021 and originated from 28 different countries. Eighty percent of the trials were randomized, with most using Holstein calves (74.5%) which were under 15 d old at the start of probiotic supplementation (71.8%). The most studied probiotics were Lactobacillus acidophilus and Enterococcus faecium. On average, supplementation lasted 50 d, and probiotics were mostly mixed into feed (88.5%). Most trials measured weight gain (88.2%) and fecal consistency (64.5%) to assess growth and health, respectively. For the second objective a scoping review and meta-analysis were conducted. It included quasi-randomized and randomized controlled trials that assessed the effects of probiotic supplementation on the growth and feed intake of dairy calves. After applying the inclusion criteria, 48 studies (49 controlled trials) were included in the study. Meta-analyses indicated that probiotics did not significantly affect total dry matter intake (DMI) or feed efficiency (FE) in dairy calves compared to controls. However, probiotic supplementation improved starter intake (P = 0.02) and average daily gain (ADG, P = 0.001) and showed a trend toward reduced milk intake (P = 0.09). Upon examining specific probiotic types, only Bacillus ssp. supplementation significantly increased ADG (P = 0.03). High and significant heterogeneity was observed for all outcomes. Meta-regression demonstrated significant associations between total DMI and probiotic type (P = 0.001) as well as the duration of supplementation (P <0.001). Additionally, meta-regression results indicated a significant association between starter intake and probiotic type (P = 0.006) and the duration of probiotic supplementation (P = 0.003). For the last objective, the antimicrobial susceptibility of 35 cattle probiotic products that claimed to contain Enterococcus spp. or Bacillus ssp. was determined. All 16 Enterococcus isolates were susceptible to chloramphenicol, streptomycin, tetracycline, tigecycline, and vancomycin. Nine Enterococcus isolates were resistant to one antibiotic (ciprofloxacin, erythromycin, penicillin, and daptomycin) and two isolates were resistant to two antibiotics. One Enterococcus isolate was multidrug-resistant to ciprofloxacin, daptomycin, and quinupristin/dalfopristin. All 15 Bacillus isolates showed susceptibility to tetracycline and vancomycin. However, one Bacillus isolate displayed resistance to chloramphenicol, and the other to erythromycin. In conclusion, the incomplete reporting across trials suggests a need for adhering to standardized guidelines in future research. While probiotic supplementation may increase ADG and starter intake in dairy calves, the existing evidence is limited due to substantial heterogeneity, and more research is needed. The results of antimicrobial susceptibility profiles emphasize the need for safety assessment in commercially available probiotics.

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