Summary of study ST000981

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 IDST000981
Study TitleMetabolomic profiles in healthy research cats receiving clindamycin with a synbiotic or a placebo: a randomized, controlled trial (Part II)
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 Date2018-06-19
Num Groups2
Total Subjects16 subjects/3 timepoints/43 samples
Study CommentsSamples from 5 cats (4 placebo, 1 synbiotic) were not available at the second timepoint due to withdrawal from treatment due to severity of gastrointestinal signs. 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 Date2019-09-23
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:SU001020
Subject Type:Other
Subject Species:Felis catus
Taxonomy ID:1758
Age Or Age Range:5-10 years
Weight Or Weight Range:3.3-6.2 kg
Gender:Male and female

Factors:

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

mb_sample_id local_sample_id Group Timepoint Gender Age at start of study (years)
SA059982160720cOEsa18_1NA NA NA -
SA059983160720cOEsa10_1NA NA NA -
SA059984160720cOEsa17_1NA NA NA -
SA059985160720cOEsa19_1NA NA NA -
SA059986160720cOEsa16_1NA NA NA -
SA059987160720cOEsa15_1NA NA NA -
SA059988160720cOEsa13_1NA NA NA -
SA059989160720cOEsa14_1NA NA NA -
SA059990160720cOEsa11_1NA NA NA -
SA059991160720cOEsa09_1NA NA NA -
SA059992160720cOEsa12_1NA NA NA -
SA059993160719cOEsa32_1Placebo Baseline (days 5-7) Female spayed 10
SA059994160718cOEsa27_1Placebo Baseline (days 5-7) Female spayed 10
SA059995160718cOEsa17_1Placebo Baseline (days 5-7) Female spayed 5
SA059996160720cOEsa02_1Placebo Baseline (days 5-7) Female spayed 5
SA059997160718cOEsa12_1Placebo Baseline (days 5-7) Female spayed 7
SA059998160718cOEsa11_1Placebo Baseline (days 5-7) Male castrated 7
SA059999160719cOEsa33_1Placebo Baseline (days 5-7) Male castrated 7
SA060000160719cOEsa31_1Placebo Baseline (days 5-7) Male castrated 9
SA060001160719cOEsa46_1Placebo Completion of treatment (days 26-28) Female spayed 5
SA060002160719cOEsa08_1Placebo Completion of treatment (days 26-28) Male castrated 7
SA060003160719cOEsa26_1Placebo Completion of treatment (days 26-28) Male castrated 7
SA060004160719cOEsa48_1Placebo Completion of treatment (days 26-28) Male castrated 9
SA060005160719cOEsa38_1Placebo Recovery (days 68-70) Female spayed 10
SA060006160719cOEsa22_1Placebo Recovery (days 68-70) Female spayed 10
SA060007160719cOEsa28_1Placebo Recovery (days 68-70) Female spayed 5
SA060008160719cOEsa45_1Placebo Recovery (days 68-70) Female spayed 5
SA060009160719cOEsa21_1Placebo Recovery (days 68-70) Female spayed 7
SA060010160718cOEsa30_1Placebo Recovery (days 68-70) Male castrated 7
SA060011160718cOEsa48_1Placebo Recovery (days 68-70) Male castrated 7
SA060012160718cOEsa08_1Placebo Recovery (days 68-70) Male castrated 9
SA060013160718cOEsa43_1Synbiotic Baseline (days 5-7) Female spayed 10
SA060014160720cOEsa08_1Synbiotic Baseline (days 5-7) Female spayed 5
SA060015160720cOEsa03_1Synbiotic Baseline (days 5-7) Male castrated 7
SA060016160719cOEsa34_1Synbiotic Baseline (days 5-7) Male castrated 9
SA060017160719cOEsa01_1Synbiotic Baseline (days 5-7) Male castrated 9
SA060018160719cOEsa40_1Synbiotic Baseline (days 5-7) Male castrated 9
SA060019160719cOEsa39_1Synbiotic Baseline (days 5-7) Male castrated 9
SA060020160718cOEsa49_1Synbiotic Baseline (days 5-7) Male castrated 9
SA060021160719cOEsa18_1Synbiotic Completion of treatment (days 26-28) Female spayed 10
SA060022160718cOEsa47_1Synbiotic Completion of treatment (days 26-28) Female spayed 5
SA060023160719cOEsa41_1Synbiotic Completion of treatment (days 26-28) Male castrated 7
SA060024160720cOEsa06_1Synbiotic Completion of treatment (days 26-28) Male castrated 9
SA060025160719cOEsa05_1Synbiotic Completion of treatment (days 26-28) Male castrated 9
SA060026160718cOEsa36_1Synbiotic Completion of treatment (days 26-28) Male castrated 9
SA060027160719cOEsa25_1Synbiotic Completion of treatment (days 26-28) Male castrated 9
SA060028160718cOEsa32_1Synbiotic Recovery (days 68-70) Female spayed 10
SA060029160720cOEsa01_1Synbiotic Recovery (days 68-70) Female spayed 5
SA060030160719cOEsa49_1Synbiotic Recovery (days 68-70) Male castrated 7
SA060031160718cOEsa37_1Synbiotic Recovery (days 68-70) Male castrated 9
SA060032160718cOEsa23_1Synbiotic Recovery (days 68-70) Male castrated 9
SA060033160718cOEsa16_1Synbiotic Recovery (days 68-70) Male castrated 9
SA060034160719cOEsa23_1Synbiotic Recovery (days 68-70) Male castrated 9
SA060035160718cOEsa42_1Synbiotic Recovery (days 68-70) Male castrated 9
Showing results 1 to 54 of 54

Collection:

Collection ID:CO001014
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 (68-70)
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:TR001034
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:75 mg, 2 capsules
Treatment Dosevolume:21 days

Sample Preparation:

Sampleprep ID:SP001027
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 AN001607
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:CH001129
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:MS001485
Analysis ID:AN001607
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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