Effects of dietary treatments and fecal microbial transplant procedures on the gastrointestinal health outcomes of dogs and cats following metronidazole administration

Martini, Sara Elizabeth

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https://hdl.handle.net/2142/129226 Copy

Description

Title

Effects of dietary treatments and fecal microbial transplant procedures on the gastrointestinal health outcomes of dogs and cats following metronidazole administration

Author(s)

Martini, Sara Elizabeth

Issue Date

2025-05-01

Director of Research (if dissertation) or Advisor (if thesis)

Swanson, Kelly S

Doctoral Committee Chair(s)

Swanson, Kelly S

Committee Member(s)

• Fahey, Jr., George C
• Dilger, Ryan N
• Suchodolski, Jan S
• Crofts, Terence S

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• antibiotic
• feline microbiome
• canine microbiome
• feline nutrition
• canine nutrition
• gastrointestinal health
• fecal microbial transplant
• microbial-derived metabolites

Abstract

Chronic enteropathies and gastrointestinal (GI) ailments may present as a combination of clinical signs but the disease etiology is often unclear, with diagnoses determined by elimination of other potential factors. The clinical signs can be addressed with steroid/immunosuppressive drugs, antibiotics, dietary interventions, and/or fecal microbial transplant (FMT) procedures. However, some of these approaches have limitations and chronic GI signs may be sustained without adequate intervention. Antibiotics are commonly administered in small animal medicine, but growing concerns of antibiotic-resistance and prolonged dysbiosis with excessive use are primary contributors for the need to evaluate alternative treatments. FMT treatments are also of growing interest, but there is a lack of standards regarding FMT application in companion animals. Dietary-focused strategies (i.e., alterations to macronutrient fractions) also have proven success in cases of food-responsive enteropathies and can alleviate some GI signs with proper diet interventions but more research is needed to optimize nutritional approaches to ensure GI remission. Therefore, the purpose of this dissertation was to evaluate the effects of dietary treatment and FMT approaches to modify and recover the gut microbiota and GI metabolite concentrations in healthy adult dogs and cats following antibiotic administration. The aim of the first experiment was to determine the effects of a low-fat GI diet on the fecal characteristics, metabolites, and microbiota concentrations of healthy adult dogs [n = 24; age = 7.38 ± 1.95 yr; body weight (BW) = 7.67 ± 0.76 kg] treated with metronidazole in an 8 wk completely randomized design study. Our second aim was identical to that of the first, with the exception that it was performed in healthy adult cats [n = 24; age = 4.77 ± 0.34 yr; BW = 4.34 ± 0.77 kg] and the GI diet was of similar fat content as compared to commercially available cat diets. During the first two experiments, all animals were fed a control diet (GBD) for 2 wk, then administered metronidazole (20 mg/kg BW) orally twice daily with meals for 2 wk. Following antibiotic cessation, animals were randomly allotted to two groups: GBD (n = 12) or BB (n = 12) and fed for another 4 wk. The test diets (BB) were commercially available veterinary diets formulated to include higher functional dietary fibers to support GI health and function. Fresh fecal and blood samples were collected at baseline, immediately following metronidazole treatment, and weekly during the 4 wk recovery phase. For the third experiment, the aim was to determine the in vitro fermentation characteristics of dietary fibers using fecal inoculum from adult dogs treated with metronidazole. Fecal samples were collected at the end of baseline (wk 2; ABX-) and antibiotic administration (wk 4; ABX+) and stabilized in a 20% glycerol solution. On the day of in vitro fermentation, fecal samples were thawed and pooled by antibiotic treatment (ABX-; ABX+) for fermentation of cellulose (negative control), pectin (positive control), beet pulp and chicory pulp over 0, 6, 12, and 18 h for measurement of pH, SCFA, and microbiota at each time point. The aim of the final experiment was to evaluate the effects of dietary fiber supplementation or FMT procedures affected the fecal characteristics, metabolite concentrations, and microbiota populations of cats [n = 25; age = 6.75 ± 1.20 yr; BW = 4.12 ± 0.66 kg] treated with metronidazole in a 13 wk completely randomized design study. Briefly, all cats were adapted to the control diet for 2 wk, administered metronidazole (20 mg/kg BW) orally twice daily with meals for 2 wk, then recovery was monitored for 4 wk. Cats were then allotted to 1 of 3 interventions [diet only (CTRL); diet+beet pulp (FIB); diet+FMT (FMT)] for 1 wk, interventions ceased and recovery was monitored for 4 wk. During intervention, cats allotted to FIB received top-dressed beet pulp (supplemented to increase total dietary fiber intake to 10% DM) at meal times and cats dosed with FMT received one prepared FMT capsule prior to food intake to ensure treatment was successfully administered. Fresh fecal samples were collected at the end of each phase and at the mid-points of recovery (d 0, 14, 28, 42, 49, 63, 77) for measurement of pH, dry matter, and metabolite concentrations. Consistently observed throughout the in vivo experiments, metronidazole increased (P<0.05) fecal scores, primary bile acids (BA), and dysbiosis index (DI) and reduced (P<0.05) fecal pH as well as several fecal metabolites [short-chain fatty acids (SCFA), branched chain fatty acids (BCFA), total phenols and indoles, ammonia, calprotectin, secondary BA, fecal fatty acids]. Over 50 bacterial genera were altered with metronidazole administration and bacterial alpha diversity measures were reduced (P<0.0001), with beta diversity plots demonstrating clustering within pre- and post- metronidazole administration. In all studies, most of the changes observed were due to recovery time, with few differences due to diet. In the first experiment, dogs consuming BB had increased (P<0.05) SCFA and immunoglobulin A concentrations compared with those consuming GBD. Dogs consuming GBD had higher (P<0.01) food intake, total phenol/indole and fecal fatty acid concentrations but lower (P<0.00001) fecal sterol concentrations than dogs consuming BB. Fecal scores reduced (more firm stools; P<0.0001) with time but were not affected with dietary interventions in dogs. Cats consuming BB had increased (P<0.05) acetate concentrations than those consuming GBD and greater decreases (P<0.05) in BW were observed in cats consuming GBD. Most variables recovered to baseline measures after 4 wk but prolonged impairment of BA conversion and dysbiosis was observed in majority of cats by the end of the study and many of the bacterial abundances failed to return to baseline measures. Recovery of over 16 bacterial genera was impacted by diet (P<0.05), but some bacterial taxa did not fully recover throughout these experiments. In the final experiment, diet had minimal effects on recovery. Fiber-supplemented cats tended to have increased fecal SCFA concentrations following intervention. Fecal characteristics improved with time, but dysbiosis was prevalent and majority of cats were able to recover with time. However, 4/25 cats still had mild dysbiosis at the end of study. In the in vitro study, antibiotic administration lowered the bacterial alpha diversity (P<0.0001), slowed pH reduction, lowered SCFA production potential, and altered SCFA molar ratios. Butyrate production was minimal among all fibers tested in tubes with ABX+ inocula. With time, increased (P<0.05) bacterial alpha diversity measures and beta-diversity shifts toward ABX- tubes was observed during beet pulp and chicory pulp fermentation but was not observed during pectin fermentation. Abundances of lactic acid bacteria, Bifidobacterium and Lactobacillus, were increased (P<0.0001) in tubes containing ABX+ inoculum during pectin or beet pulp fermentation while increased (P<0.0001) abundances of SCFA-producing bacteria, Faecalibacterium and Bacteroides, were observed in ABX- inocula tubes during chicory pulp fermentation. Our findings indicate that metronidazole is a powerful antibiotic that reduces microbial abundances and bacterial diversity, significantly altering microbial metabolism. Dietary intervention was able to improve fecal characteristics, microbiota, and metabolite concentrations to some extent. The in vitro fermentation data suggests that fermentable fibers may be useful in shifting GI microbiota prior to or following antibiotic administration. Oral FMT treatment elicited rapid benefits, but recovery was only monitored up to 4 wk and should be longitudinally monitored in animals with GI enteropathies as disease relapse may occur. In conclusion, incorporation of targeted dietary intervention strategies into treatment plans of animals with diagnosed GI enteropathies may promote quicker microbial recovery, ultimately supporting faster recovery of overall host health in companion animals undergoing antibiotic treatment.

Graduation Semester

2025-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129226

Copyright and License Information

Copyright 2025 Sara E. Martini

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