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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST000981 |
| Study Title | Metabolomic profiles in healthy research cats receiving clindamycin with a synbiotic or a placebo: a randomized, controlled trial (Part II) |
| Study Type | Double-blind randomized controlled trial |
| Study 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 California, Davis |
| Department | Genome and Biomedical Sciences Facility |
| Laboratory | WCMC Metabolomics Core |
| Last Name | Fiehn |
| First Name | Oliver |
| Address | 1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616 |
| ofiehn@ucdavis.edu | |
| Phone | (530) 754-8258 |
| Submit Date | 2018-06-19 |
| Num Groups | 2 |
| Total Subjects | 16 subjects/3 timepoints/43 samples |
| Study Comments | Samples 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 Available | Yes |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | GC-MS |
| Release Date | 2019-09-23 |
| Release Version | 1 |
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: | 9685 |
| 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) |
|---|---|---|---|---|---|
| SA059982 | 160720cOEsa18_1 | NA | NA | NA | - |
| SA059983 | 160720cOEsa10_1 | NA | NA | NA | - |
| SA059984 | 160720cOEsa17_1 | NA | NA | NA | - |
| SA059985 | 160720cOEsa19_1 | NA | NA | NA | - |
| SA059986 | 160720cOEsa16_1 | NA | NA | NA | - |
| SA059987 | 160720cOEsa15_1 | NA | NA | NA | - |
| SA059988 | 160720cOEsa13_1 | NA | NA | NA | - |
| SA059989 | 160720cOEsa14_1 | NA | NA | NA | - |
| SA059990 | 160720cOEsa11_1 | NA | NA | NA | - |
| SA059991 | 160720cOEsa09_1 | NA | NA | NA | - |
| SA059992 | 160720cOEsa12_1 | NA | NA | NA | - |
| SA059993 | 160719cOEsa32_1 | Placebo | Baseline (days 5-7) | Female spayed | 10 |
| SA059994 | 160718cOEsa27_1 | Placebo | Baseline (days 5-7) | Female spayed | 10 |
| SA059995 | 160718cOEsa17_1 | Placebo | Baseline (days 5-7) | Female spayed | 5 |
| SA059996 | 160720cOEsa02_1 | Placebo | Baseline (days 5-7) | Female spayed | 5 |
| SA059997 | 160718cOEsa12_1 | Placebo | Baseline (days 5-7) | Female spayed | 7 |
| SA059998 | 160718cOEsa11_1 | Placebo | Baseline (days 5-7) | Male castrated | 7 |
| SA059999 | 160719cOEsa33_1 | Placebo | Baseline (days 5-7) | Male castrated | 7 |
| SA060000 | 160719cOEsa31_1 | Placebo | Baseline (days 5-7) | Male castrated | 9 |
| SA060001 | 160719cOEsa46_1 | Placebo | Completion of treatment (days 26-28) | Female spayed | 5 |
| SA060002 | 160719cOEsa08_1 | Placebo | Completion of treatment (days 26-28) | Male castrated | 7 |
| SA060003 | 160719cOEsa26_1 | Placebo | Completion of treatment (days 26-28) | Male castrated | 7 |
| SA060004 | 160719cOEsa48_1 | Placebo | Completion of treatment (days 26-28) | Male castrated | 9 |
| SA060005 | 160719cOEsa38_1 | Placebo | Recovery (days 68-70) | Female spayed | 10 |
| SA060006 | 160719cOEsa22_1 | Placebo | Recovery (days 68-70) | Female spayed | 10 |
| SA060007 | 160719cOEsa28_1 | Placebo | Recovery (days 68-70) | Female spayed | 5 |
| SA060008 | 160719cOEsa45_1 | Placebo | Recovery (days 68-70) | Female spayed | 5 |
| SA060009 | 160719cOEsa21_1 | Placebo | Recovery (days 68-70) | Female spayed | 7 |
| SA060010 | 160718cOEsa30_1 | Placebo | Recovery (days 68-70) | Male castrated | 7 |
| SA060011 | 160718cOEsa48_1 | Placebo | Recovery (days 68-70) | Male castrated | 7 |
| SA060012 | 160718cOEsa08_1 | Placebo | Recovery (days 68-70) | Male castrated | 9 |
| SA060013 | 160718cOEsa43_1 | Synbiotic | Baseline (days 5-7) | Female spayed | 10 |
| SA060014 | 160720cOEsa08_1 | Synbiotic | Baseline (days 5-7) | Female spayed | 5 |
| SA060015 | 160720cOEsa03_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 7 |
| SA060016 | 160719cOEsa34_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 9 |
| SA060017 | 160719cOEsa01_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 9 |
| SA060018 | 160719cOEsa40_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 9 |
| SA060019 | 160719cOEsa39_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 9 |
| SA060020 | 160718cOEsa49_1 | Synbiotic | Baseline (days 5-7) | Male castrated | 9 |
| SA060021 | 160719cOEsa18_1 | Synbiotic | Completion of treatment (days 26-28) | Female spayed | 10 |
| SA060022 | 160718cOEsa47_1 | Synbiotic | Completion of treatment (days 26-28) | Female spayed | 5 |
| SA060023 | 160719cOEsa41_1 | Synbiotic | Completion of treatment (days 26-28) | Male castrated | 7 |
| SA060024 | 160720cOEsa06_1 | Synbiotic | Completion of treatment (days 26-28) | Male castrated | 9 |
| SA060025 | 160719cOEsa05_1 | Synbiotic | Completion of treatment (days 26-28) | Male castrated | 9 |
| SA060026 | 160718cOEsa36_1 | Synbiotic | Completion of treatment (days 26-28) | Male castrated | 9 |
| SA060027 | 160719cOEsa25_1 | Synbiotic | Completion of treatment (days 26-28) | Male castrated | 9 |
| SA060028 | 160718cOEsa32_1 | Synbiotic | Recovery (days 68-70) | Female spayed | 10 |
| SA060029 | 160720cOEsa01_1 | Synbiotic | Recovery (days 68-70) | Female spayed | 5 |
| SA060030 | 160719cOEsa49_1 | Synbiotic | Recovery (days 68-70) | Male castrated | 7 |
| SA060031 | 160718cOEsa37_1 | Synbiotic | Recovery (days 68-70) | Male castrated | 9 |
| SA060032 | 160718cOEsa23_1 | Synbiotic | Recovery (days 68-70) | Male castrated | 9 |
| SA060033 | 160718cOEsa16_1 | Synbiotic | Recovery (days 68-70) | Male castrated | 9 |
| SA060034 | 160719cOEsa23_1 | Synbiotic | Recovery (days 68-70) | Male castrated | 9 |
| SA060035 | 160718cOEsa42_1 | Synbiotic | 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 (30m 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 (30m 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 |
