Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea

Abstract

Background and aims Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis. Methods A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing. Results and conclusions As expected, healthy horses at both locations showed a greater α-diversity and lower β-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater α-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4±3 grades), compared to untreated horses (median: 1.5±3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53±0.27) than untreated horses (0.62±0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.

Changes in the Fecal Microbiota Associated with a Broad-Spectrum Antimicrobial Administration in Hospitalized Neonatal Foals with Probiotics Supplementation

“…Notably, three of the four foals received one to three fecal microbiota transplantations (FMT) during the course of diarrhea, which was considered effective in all cases. While the use of FMT in adult horses with diarrhea has been recently evaluated by means of NGS [73], to the authors knowledge, there is no peer-reviewed literature on the efficacy of FMT in neonatal foals [74]. McKinney et al (2021) reported that FMT proved an effective treatment to reduce diarrhea severity in horses with colitis and to improve microbiome diversity [73].…”

“…While the use of FMT in adult horses with diarrhea has been recently evaluated by means of NGS [73], to the authors knowledge, there is no peer-reviewed literature on the efficacy of FMT in neonatal foals [74]. McKinney et al (2021) reported that FMT proved an effective treatment to reduce diarrhea severity in horses with colitis and to improve microbiome diversity [73]. While it is very likely that FMT had influenced the findings and represent a main confounding factor, an effect of FMT on fecal microbiota dynamic was not possible to be discriminated in this study.…”

Gut Microbiota Manipulation in Foals—Naturopathic Diarrhea Management, or Unsubstantiated Folly?

“…A small 2014 study of horses with antibiotic-induced or undifferentiated colitis reported improved fecal consistency following FMT in three out of four recipients [29]. These results are supported by a larger and more recent study by McKinney et al, which assessed the clinical and microbiota responses to FMT in 12 hospitalized adult horses with colitis [55]. Prior to treatment, researchers found lower alpha-diversity and higher beta-diversity of the fecal microbiota of horses with colitis.…”

“…In a similar vein, prebiotics are “substrate that is selectively utilized by host microorganisms conferring a health benefit” [ 53 ]. Based on the same principles, but taking a more comprehensive approach, FMT involves transfer of fecal suspension from a healthy donor to the bowel of a recipient [ 15 ], and successful applications in human medicine have understandably piqued interest in the veterinary community [ 29 , 54 , 55 ].…”

Highlights of recent clinically relevant papers

“…This study by Caroline McKinney and co ‐ workers in the USA assessed faecal microbial transplantation (FMT) as a treatment and modulator of faecal microbiota in horses with colitis .…”