Summary of study ST000979

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000669. The data can be accessed directly via it's Project DOI: 10.21228/M86D65 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000979
Study TitleMetabolomic profiles in healthy research cats receiving clindamycin with a synbiotic or a placebo: a randomized, controlled trial (Part I)
Study TypeDouble-blind randomized controlled trial
Study SummaryAntibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic. Methods. 16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (8 cats) or commercially-available synbiotic (8 cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last 3 days of baseline (days 5-7), treatment (26-28), and recovery (631-633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P<0.05 was considered significant. The Benjamini & Hochberg’s False Discovery Rate was used to adjust for multiple comparisons. Results. Median age was 6 and 5 years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26-28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631-633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups. Discussion. Cats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2018-06-15
Num Groups2
Total Subjects16 subjects/3 timepoints/47 samples
Study CommentsSamples from 1 subject lacking for one timepoint, resulting in a total of 47 samples. Genomic DNA was extracted from 100 mg of feces from each pooled sample using a commercially available kit (PowerSoil®, Mo Bio, Carlsbad, CA USA) according to manufacturer’s protocol for a total of 11 pooled samples.
Raw Data AvailableYes
Raw Data File Type(s).cdf
Analysis Type DetailGC-MS
Release Date2018-07-17
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M86D65
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000669
Project DOI:doi: 10.21228/M86D65
Project Title:Metabolomic profiles in healthy research cats receiving clindamycin with a synbiotic or a placebo: a randomized, controlled trial
Project Type:Double-blind randomized controlled trial
Project Summary:Antibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic. Methods. 16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (8 cats) or commercially-available synbiotic (8 cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last 3 days of baseline (days 5-7), treatment (26-28), and recovery (631-633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P<0.05 was considered significant. The Benjamini & Hochberg’s False Discovery Rate was used to adjust for multiple comparisons. Results. Median age was 6 and 5 years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26-28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631-633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups. Discussion. Cats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.
Institute:University of Tennessee
Department:Small Animal Clinical Sciences, , College of Veterinary Medicine
Last Name:Whittemore
First Name:Jacqueline
Address:2407 River Drive, Knoxville TN 37996
Email:jwhittemore@utk.edu
Phone:865-974-8387
Funding Source:University of Tennessee, College of Veterinary Medicine Companion Animal Fund; University of Tennessee, College of Veterinary Medicine Center of Excellence in Livestock Diseases and Human Health Summer Research Program; Nutramax Laboratories Veterinary Sciences, Inc., Lancaster, SC

Subject:

Subject ID:SU001018
Subject Type:Animal
Subject Species:Felis catus
Taxonomy ID:1758
Age Or Age Range:3-8 years
Weight Or Weight Range:3.4-5.8 kg
Gender:Male and female

Factors:

Subject type: Animal; Subject species: Felis catus (Factor headings shown in green)

mb_sample_id local_sample_id Group Timepoint Gender Age at start of study
SA059899160720cOEsa16_1NA NA NA -
SA059900160720cOEsa17_1NA NA NA -
SA059901160720cOEsa18_1NA NA NA -
SA059902160720cOEsa14_1NA NA NA -
SA059903160720cOEsa13_1NA NA NA -
SA059904160720cOEsa09_1NA NA NA -
SA059905160720cOEsa10_1NA NA NA -
SA059906160720cOEsa11_1NA NA NA -
SA059907160720cOEsa12_1NA NA NA -
SA059908160720cOEsa19_1NA NA NA -
SA059909160720cOEsa15_1NA NA NA -
SA059910160718cOEsa28_1Placebo Baseline (days 5-7) Female spayed 3
SA059911160718cOEsa18_1Placebo Baseline (days 5-7) Female spayed 6
SA059912160718cOEsa04_1Placebo Baseline (days 5-7) Female spayed 7
SA059913160719cOEsa47_1Placebo Baseline (days 5-7) Female spayed 8
SA059914160718cOEsa39_1Placebo Baseline (days 5-7) Male castrated 5
SA059915160718cOEsa13_1Placebo Baseline (days 5-7) Male castrated 5
SA059916160718cOEsa01_1Placebo Baseline (days 5-7) Male castrated 6
SA059917160718cOEsa46_1Placebo Baseline (days 5-7) Male castrated 6
SA059918160719cOEsa35_1Placebo Completion of treatment (days 26-28) Female spayed 3
SA059919160720cOEsa04_1Placebo Completion of treatment (days 26-28) Female spayed 6
SA059920160718cOEsa07_1Placebo Completion of treatment (days 26-28) Female spayed 7
SA059921160718cOEsa35_1Placebo Completion of treatment (days 26-28) Female spayed 8
SA059922160718cOEsa20_1Placebo Completion of treatment (days 26-28) Male castrated 5
SA059923160718cOEsa50_1Placebo Completion of treatment (days 26-28) Male castrated 5
SA059924160719cOEsa13_1Placebo Completion of treatment (days 26-28) Male castrated 6
SA059925160719cOEsa20_1Placebo Completion of treatment (days 26-28) Male castrated 6
SA059926160718cOEsa15_1Placebo Recovery (days 631-633) Female spayed 3
SA059927160720cOEsa05_1Placebo Recovery (days 631-633) Female spayed 6
SA059928160718cOEsa02_1Placebo Recovery (days 631-633) Female spayed 7
SA059929160719cOEsa16_1Placebo Recovery (days 631-633) Female spayed 8
SA059930160718cOEsa19_1Placebo Recovery (days 631-633) Male castrated 5
SA059931160719cOEsa24_1Placebo Recovery (days 631-633) Male castrated 5
SA059932160718cOEsa21_1Placebo Recovery (days 631-633) Male castrated 6
SA059933160719cOEsa04_1Placebo Recovery (days 631-633) Male castrated 6
SA059934160718cOEsa41_1Synbiotic Baseline (days 5-7) Female spayed 3
SA059935160718cOEsa38_1Synbiotic Baseline (days 5-7) Female spayed 6
SA059936160718cOEsa29_1Synbiotic Baseline (days 5-7) Female spayed 8
SA059937160718cOEsa14_1Synbiotic Baseline (days 5-7) Male castrated 3
SA059938160718cOEsa44_1Synbiotic Baseline (days 5-7) Male castrated 5
SA059939160719cOEsa37_1Synbiotic Baseline (days 5-7) Male castrated 5
SA059940160718cOEsa09_1Synbiotic Baseline (days 5-7) Male castrated 5
SA059941160718cOEsa05_1Synbiotic Baseline (days 5-7) Male castrated 6
SA059942160719cOEsa06_1Synbiotic Completion of treatment (days 26-28) Female spayed 3
SA059943160718cOEsa31_1Synbiotic Completion of treatment (days 26-28) Female spayed 6
SA059944160719cOEsa12_1Synbiotic Completion of treatment (days 26-28) Female spayed 8
SA059945160718cOEsa40_1Synbiotic Completion of treatment (days 26-28) Male castrated 3
SA059946160719cOEsa11_1Synbiotic Completion of treatment (days 26-28) Male castrated 5
SA059947160718cOEsa24_1Synbiotic Completion of treatment (days 26-28) Male castrated 5
SA059948160718cOEsa10_1Synbiotic Completion of treatment (days 26-28) Male castrated 5
SA059949160718cOEsa22_1Synbiotic Completion of treatment (days 26-28) Male castrated 6
SA059950160718cOEsa25_1Synbiotic Recovery (days 631-633) Female spayed 3
SA059951160719cOEsa19_1Synbiotic Recovery (days 631-633) Female spayed 6
SA059952160719cOEsa07_1Synbiotic Recovery (days 631-633) Female spayed 8
SA059953160719cOEsa29_1Synbiotic Recovery (days 631-633) Male castrated 3
SA059954160719cOEsa17_1Synbiotic Recovery (days 631-633) Male castrated 5
SA059955160719cOEsa14_1Synbiotic Recovery (days 631-633) Male castrated 5
SA059956160719cOEsa36_1Synbiotic Recovery (days 631-633) Male castrated 6
Showing results 1 to 58 of 58

Collection:

Collection ID:CO001012
Collection Summary:First-morning naturally-voided feces were collected daily on the last 3 days of baseline (days 5-7), treatment (26-28), and recovery (631-633)
Sample Type:Feces
Collection Method:Natural voiding
Collection Frequency:Daily
Collection Duration:3 days of each time period
Volumeoramount Collected:1 gm
Storage Conditions:-80℃
Collection Vials:2 mL screw cap polypropylene vials
Storage Vials:2 mL screw cap polypropylene vials
Collection Tube Temp:Room temperature
Additives:None

Treatment:

Treatment ID:TR001032
Treatment Summary:The placebo treatment group was administered Clindamycin orally with a placebo once daily for 21 days with reevaluation 603 days thereafter. The synbiotic treatment group was administered Clindamycin orally with a commercially-available synbiotic (Proviable DC) once daily for 21 days with reevaluation 603 days thereafter.
Treatment Compound:Clindamycin, placebo (Placebo treatment group); Clindamycin, Proviable DC (Synbiotic treatment group)
Treatment Route:PO
Treatment Dose:150 mg, 1 capsule
Treatment Dosevolume:21 days

Sample Preparation:

Sampleprep ID:SP001025
Sampleprep Summary:Samples were immediately frozen and remained in storage at -80ºC pending completion of data collection. Samples for each cat from each timepoint were combined directly prior to sample analysis to generate pooled samples for analysis. Genomic DNA was extracted from 100 mg of feces from each pooled sample using a commercially available kit (PowerSoil®, Mo Bio, Carlsbad, CA USA) according to manufacturer’s protocol. 10 mg of lyophilized feces from each pooled sample were used for metabolomic analyses.
Processing Method:Lyophilization

Combined analysis:

Analysis ID AN001603
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus 4D GC
Column Restek Rtx-5Sil MS (30 x 0.25mm, 0.25um)
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode POSITIVE
Units Counts

Chromatography:

Chromatography ID:CH001125
Instrument Name:Leco Pegasus 4D GC
Column Name:Restek Rtx-5Sil MS (30 x 0.25mm, 0.25um)
Column Pressure:7.7 PSI (initial condition)
Column Temperature:50 - 330°C
Flow Rate:1 ml/min
Injection Temperature:50°C ramped to 250°C by 12°C/s
Sample Injection:0.5 uL
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
Transferline Temperature:230°C
Washing Buffer:Ethyl Acetate
Sample Loop Size:30 m length x 0.25 mm internal diameter
Randomization Order:Excel generated
Chromatography Type:GC

MS:

MS ID:MS001481
Analysis ID:AN001603
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC-TOF
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250°C
Ionization Energy:70eV
Mass Accuracy:Nominal
Scan Range Moverz:85-500
Scanning Cycle:17 Hz
Scanning Range:80-500 Da
Skimmer Voltage:1850
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