M Lee 1 M Questa 1 B Weimer 1 J Lidbury 2 J Steiner 2 J Suchodolski 2 S Marsilio 1 1 UC Davis School of Veterinary Medicine Davis California ID: 1036069
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1. Peripheral immune modulation, temporal dynamics, and community shifts of the healthy canine gut microbiome after fecal microbiota transplantationM. Lee1, M. Questa1, B. Weimer1, J. Lidbury2, J. Steiner2, J. Suchodolski2, S. Marsilio11UC Davis School of Veterinary Medicine, Davis, California2Texas A&M Gastrointestinal Laboratory
2. BackgroundFecal Microbiota Transplantation (FMT) Kelly et al. Gastroenterology. 2015Fecal Transplantfrom DonorDiseased GutDysbiosisHealthy GutNormobiosis
3. BackgroundACG strongly recommends FMT treatment for recurrent C. difficile Placebo controlled study in canine parvovirus FMT superior to standard treatment aloneFMT performed in sick patients and ill-defined disease groups (IBD)Poorly understood mechanisms of action, determinants of engraftment, and immune modulationWhole metagenomic sequencing (WGS) allows species and strain level analysis to track microbial alterations and engraftmentSmillie, et al. Cell host & microbe 2018Chaitman & Gaschen Vet. Clin. N. Am. 2021Kelly et al. Am J Gastroenterol 2021
4. AimsCharacterize the microbial community shifts, temporal dynamics, and peripheral immune modulation following FMT in healthy dogsIdentify factors within the microbiome predicting FMT engraftment in healthy dogs
5. Material and MethodsInclusion criteriaRecipients: 10 clinically healthy, client-owned dogsDonors: 2 clinically healthy, client-owned dogsExclusion criteriaGI signs (vomiting, diarrhea, hyporexia, weight loss) past six monthsKnown microbiome-altering medications past six monthsOther systemic diseases
6. Day 0 FMT Day 1 post-FMTDay 4 post-FMTDay 10 post-FMTDay 28 post-FMT Feces (DI, WGS)Blood (CBC, chemistry,Flow cytometryCRP, cytokines)Feces (DI, WGS)Blood (CBC, chemistry,Flow cytometryCRP, cytokines)Clinical surveyMaterial and Methods 10 clinically healthy dogs received 5g/kg FMT via rectal enema
7. Results: ClinicalFMT well tolerated with no known major side effects Normal appetite3 animals experienced transient diarrhea post-FMT3 cases of vomiting (2 on day 1, 1 on day 28 post-FMT)1 case of vomiting and 1 case of diarrhea due to dietary indiscretion
8. Results: Clinical
9. Results: Peripheral Immune ModulationStatistical analysisD’Agostino & Pearson, Mixed effects model ANOVAComplete Blood CountAll values not significantly different between days 0, 1, 4, 10, 28Serum biochemistry Anion Gap (p = 0.0057) & bicarbonate (p = 0.016) statistically significantFalse Discovery Rate adjustment via Benjamini-Hochberg methodAdjusted p values: Anion Gap (p = 0.13), bicarbonate (p = 0.18)
10. Results: Peripheral Immune Modulation CBC Chemistry panelC-Reactive ProteinCytokinesNo change
11. Results: Peripheral Immune Modulation
12. Results: WGSWhole metagenomic shotgun sequencingEngraftment7093 SPECIESDonorRecipientFMTRecipientPre-FMT Day 0Post-FMTDays 1, 4, 10, 286289 Bacteria (89%)424 Viruses (6%)280 Archaea (4%)58 Fungi (0.8%)29 Chromista (0.4%)
13. Results: WGS
14. Results: WGS
15. DiscussionOne-time rectal enema FMT in healthy dogs is relatively safeFMT in healthy dogs do not lead to significant changes in the peripheral immune system markers measured in the studyCRPCytokinesCBCSerum biochemistrySpecies level engraftment seen but factors not yet known
16. What’s next + LimitationsMultivariate statistics for population diversity and taxonomyCompare pre- and post-FMT shifts, ID engraftment factorsFlow cytometry analysis on lymphocyte populationFuture FMT study in dogs with chronic enteropathySmall sample size, some dogs with mild clinical and/or laboratory abnormalities
17. AcknowledgementSpecial thank you to:Comparative Gastroenterology Society and IDEXX Laboratories, Inc. for Veterinary Summer Student Scholar Award Texas A&M GI Lab for their generous help in measuring blood and fecal samples
18. Questions?
19. ContactMary Ann LeeDoctor of Veterinary Medicine CandidateUC Davis School of Veterinary Medicine1 Garrod DriveDavis, CA 95616Email: mjrlee@ucdavis.ed