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Simple Summary: Acute hemorrhagic diarrhea syndrome (AHDS) is characterized by severe gastrointestinal fluid loss and necrotizing enteritis. This indicates an intestinal barrier dysfunction, altered intestinal permeability may indicate disease severity and might represent a risk factor for the development of chronic disorders. Serum iohexol measurement is utilized to assess intestinal permeability in dogs. Our study aimed to correlate intestinal permeability (measured by serum iohexol concentration (SIC)) with clinical severity in dogs with AHDS. We hypothesized increased intestinal permeability in dogs with AHDS, correlating with clinical severity. Fifty-three client-owned dogs, including those with AHDS and healthy controls, were enrolled. Clinical severity was assessed using the AHDS index and criteria for systemic inflammatory response syndrome (SIRS). Simultaneously, dogs were orally administered iohexol, and serum samples were collected for SIC measurement. The findings revealed significantly elevated SIC among dogs with AHDS compared to healthy controls, with a positive correlation between SIC and disease severity indices. These results highlight that dogs with a severe form of AHDS have an especially significant dysfunction of the intestinal barrier. Future studies are necessary to evaluate a potential association between an altered intestinal barrier at the phase of acute enteritis and the development of chronic intestinal disease later in life. Histopathologic examination of intestinal biopsies from dogs with acute hemorrhagic diarrhea syndrome (AHDS) reveals necrotizing enteritis and epithelial integrity loss. Serum iohexol measurement has been utilized to assess intestinal permeability. Our hypothesis is that dogs with AHDS have increased intestinal permeability, which is associated with the severity of clinical signs. In this prospective case–control study, 53 client-owned dogs (28 AHDS, 25 healthy controls) were evaluated. Clinical severity was assessed using the AHDS index and systemic inflammatory response syndrome (SIRS) criteria. Simultaneously, dogs received oral iohexol, and serum iohexol concentrations (SICs) were measured two hours later. Results indicated significantly higher (p = 0.002) SIC in AHDS dogs (median: 51 µg/mL; min–max: 9–246) than in healthy controls (30 µg/mL; 11–57). There was a significant positive correlation between AHDS index and SIC (rS = 0.4; p = 0.03) and a significant negative between SIC and serum albumin concentrations (Pearson r = −0.55; p = 0.01). Dogs with severe AHDS (mean 106 µg/mL; range: 17–246) demonstrated significantly higher (p = 0.002) SIC than those with mild to moderate disease (29 µg/mL; 9–54). These findings underscore the association between intestinal permeability and clinical severity in dogs with AHDS assessed by iohexol. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to examine the diagnostic sensitivity of 3-bromotyrosine (3-BrY) and compare serum and fecal 3-BrY concentrations between dogs with chronic inflammatory enteropathy (CIE) that showed pathological changes in biopsy samples of the gastrointestinal (GI) tract. A weak correlation was found between serum C-reactive protein and serum 3-BrY concentrations, but no correlation was observed between the canine chronic enteropathy clinical activity index and serum or fecal 3-BrY concentrations. No significant difference in 3-BrY concentrations was found in biological samples between dogs with CIE who had various GI pathological changes. It is worth noting that dogs with CIE often have increased 3-BrY concentrations in both their serum and fecal samples. However, these 3-BrY elevations may not accurately reflect the severity of GI histological findings. Chronic inflammatory enteropathies (CIEs) in dogs involve the infiltration of gastrointestinal tissue with inflammatory cells. This study aimed to assess the sensitivity of serum and fecal 3-bromotyrosine (3-BrY) concentrations in dogs with CIE. The difference in 3-BrY concentrations in dogs with different gastrointestinal (GI) pathological changes was also assessed. In total, 68 dogs with CIE were enrolled in the study. The median serum 3-BrY concentration was 3.3 µmol/L, while the median 3-day mean and maximum fecal 3-BrY concentrations were 38.9 and 63.2 mmol/g of feces, respectively. The median serum C-reactive protein concentration was 45.0 mg/L. The median 3-day mean and maximum fecal α1-proteinase inhibitor concentrations were 6.1 and 9 µg/g of feces, respectively. Increased 3-BrY concentrations were observed in 90.9% of CIE dogs based on serum concentrations, 75.8% based on mean fecal concentrations, and 69.4% based on maximum fecal concentrations. A weak correlation (ρ = 0.31, p < 0.0118) was found between serum CRP and serum 3-BrY concentrations. There was no correlation between the canine chronic enteropathy clinical activity index and serum or fecal 3-BrY concentrations (p > 0.05). Additionally, no significant difference in serum or fecal 3-BrY concentrations was found among CIE dogs with different GI pathological changes (p > 0.05). In conclusion, dogs with CIE have increased 3-BrY concentrations in serum and fecal samples. However, 3-BrY concentrations may not accurately indicate the severity of gastrointestinal inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic enteropathy (CE) is a spectrum of chronic digestive disorders in cats. Understanding the metabolic dysfunction in the gut is crucial for understanding these diseases and developing better treatment options. However, the specific metabolic profiles of cats with CE remain largely unexplored. As fat is an essential energy source that participates in many physiological pathways, we focused on fat-related metabolites in this study. Fecal samples from cats with CE and healthy cats were collected, and concentrations of various fatty acids, sterols, and bile acids were measured. Cats with CE had higher concentrations of fatty acids, increased concentrations of animal-based sterols, and decreased plant-based sterols in their feces. A subset of cats with CE also showed abnormal bile acid metabolism, i.e., an increased percentage of primary bile acids. These findings suggest that cats with CE may have altered fat metabolism in their digestive tracts. Chronic enteropathy (CE) in cats encompasses food-responsive enteropathy, chronic inflammatory enteropathy (or inflammatory bowel disease), and low-grade intestinal T-cell lymphoma. While alterations in the gut metabolome have been extensively studied in humans and dogs with gastrointestinal disorders, little is known about the specific metabolic profile of cats with CE. As lipids take part in energy storage, inflammation, and cellular structure, investigating the lipid profile in cats with CE is crucial. This study aimed to measure fecal concentrations of various fatty acids, sterols, and bile acids. Fecal samples from 56 cats with CE and 77 healthy control cats were analyzed using gas chromatography-mass spectrometry, targeting 12 fatty acids, 10 sterols, and 5 unconjugated bile acids. Fecal concentrations of nine targeted fatty acids and animal-derived sterols were significantly increased in cats with CE. However, fecal concentrations of plant-derived sterols were significantly decreased in cats with CE. Additionally, an increased percentage of primary bile acids was observed in a subset of cats with CE. These findings suggest the presence of lipid maldigestion, malabsorption, and inflammation in the gastrointestinal tract of cats with CE. Understanding the lipid alterations in cats with CE can provide insights into the disease mechanisms and potential future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Untargeted shotgun DNA sequencing of fecal samples is a relatively novel approach to study the microbiome. This method allows better classification of bacteria on a species level compared to traditional 16S rRNA gene sequencing, and provides data about viruses, fungi, archaea, and functional genes. A targeted qPCR-based dysbiosis index has been recently introduced to evaluate the fecal microbiota in dogs. This study evaluated the agreement for core bacterial taxa between targeted qPCR assays and relative abundances obtained by shotgun DNA sequencing. We analyzed the fecal microbiota of 296 dogs with various clinical phenotypes using both methods. Significant correlations were found between the two methods, and the qPCR-based dysbiosis index accurately reflected shifts in the microbiome of dogs as observed by DNA shotgun sequencing. DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of Clostridioides (C.) difficile on gut diseases in dogs is a subject of debate. In people, an imbalance in bile acids in the gut is often linked to the presence of C. difficile. This study examined the relationship between an imbalance in the gut bacteria (altered dysbiosis index and decreased C. hiranonis) and the presence of C. difficile in dogs. We looked at the following four different groups: dogs with digestive issues (submitted samples and those with long-term or short-term diarrhea) and healthy dogs. Our results showed that dogs with C. difficile often had a greater imbalance in gut bacteria and less of another type of bacteria (C. hiranonis). Importantly, regardless of whether dogs were carriers of C. difficile, this did not influence how well dogs responded to treatments for digestive problems. This suggests that, in dogs, the presence of C. difficile does not require special treatment. In short, while C. difficile is associated with microbiota dysbiosis and lower levels of C. hiranonis in dogs, its presence does not require changes in routine treatment. The role of Clostridioides (C.) difficile as an enteropathogen in dogs is controversial. In humans, intestinal bile acid-dysmetabolism is associated with C. difficile prevalence. The relationship between fecal qPCR-based dysbiosis index (DI) and especially the abundance of bile acid-converting Clostridium hiranonis with the presence of C. difficile in dogs was explored across the following 4 cohorts: 358 fecal samples submitted for routine diagnostic work-up, 33 dogs with chronic enteropathy, 14 dogs with acute diarrhea, and 116 healthy dogs. Dogs that tested positive for C. difficile had significantly higher DI (median, 4.4 (range from 0.4 to 8.6)) and lower C. hiranonis (median, 0.1 (range from 0.0 to 7.5) logDNA/g) than dogs that tested negative for C. difficile (median DI, −1 (range from −7.2 to 8.9); median C. hiranonis abundance, 6.2 (range from 0.1 to 7.5) logDNA/g; p < 0.0001, respectively). In 33 dogs with CE and 14 dogs with acute diarrhea, the treatment response did not differ between C. difficile-positive and -negative dogs. In the group of clinically healthy dogs, 9/116 tested positive for C. difficile, and 6/9 of these had also an abnormal DI. In conclusion, C. difficile is strongly linked to intestinal dysbiosis and lower C. hiranonis levels in dogs, but its presence does not necessitate targeted treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Similar to humans, dogs are affected by a variety of liver diseases with various causes and presentations. Recently, growing interest has focused on measuring markers of oxidative stress in patients with liver disease; however, no study to date has compared markers of oxidative stress between dogs with different liver diseases. This study aimed to evaluate markers of oxidative stress in dogs with different types of liver disease by measuring a compound known as 15-F2t-isoprostane in their urine. Among dogs with one of three different types of liver diseases, only those with a congenital portosystemic shunt (CPSS) had a significant increase in this oxidative stress marker when compared with a group of healthy control dogs. Isoprostanes are stable end products of lipid peroxidation that can be used as markers of oxidative stress. It was previously reported that a cohort of dogs with various liver diseases had increased urinary isoprostane concentrations compared to healthy control (HC) dogs. The aim of this study was to measure and report urinary isoprostane concentrations in dogs with different types of liver diseases. Urine was collected from 21 HC dogs and from 40 dogs with liver disease, including 25 with chronic hepatitis (CH), 7 with steroid hepatopathy (SH), and 8 with a congenital portosystemic shunt (CPSS). In this prospective, observational study, urinary 15-F2t-isoprostane (F2-IsoP) concentrations were measured by liquid chromatography/mass spectrometry and normalized to urinary creatinine concentrations. Concentrations were compared between groups using a Kruskal–Wallis test followed by Dunn's multiple comparisons tests. Significance was set at p < 0.05. The median (range) urinary F2-IsoP to creatinine ratios (ng/mg UCr) were 3.6 (2.2–12.4) for HC dogs, 5.7 (2.4–11.3) for dogs with CH, 4.8 (2.4–8.6) for dogs with SH, and 12.5 (2.9–22.9) for dogs with CPSS. CPSS dogs had significantly higher urinary F2-IsoP concentrations than HC dogs (p = 0.004), suggesting increased oxidative stress among this cohort. [ABSTRACT FROM AUTHOR]

Amino acids play an important role in metabolism. Comprehensive analytical validation of an assay for the concurrent measurement of a large number of amino acids in dogs is lacking, which precludes its usefulness in a clinical setting. Amino acids are often measured in plasma or whole blood. However, serum is commonly used for gastrointestinal diagnostic testing in dogs and is therefore convenient to use. This study aimed to analytically validate an assay for the concurrent measurement of amino acids in dog serum and to evaluate differences in amino acid concentrations in whole blood, plasma, and serum in dogs. Analytical validation of the assay (Biochrom 30+ Amino Acid Analyzer) was performed on fresh or banked serum samples from dogs. Whole blood, plasma, and serum from 36 healthy dogs were analyzed, and concentrations of the three sample types were compared. The assay was demonstrated to be precise, reproducible, accurate, linear, and stable for the measurement of the majority of compounds detected in dog serum. Cystine, glutamic acid, and ethanolamine were shown to be unstable at conditions commonly encountered in clinical settings. Significant differences in concentrations were identified between whole blood, plasma, and serum for 33 of 42 compounds. Amino acid profiles in serum and plasma were more similar to each other than to those in whole blood. While some amino acids are present in similar concentrations in whole blood, plasma, and serum, others are highly dependent on the type of biofluid, and measurements warrant strict adherence to sample type-based reference intervals. [ABSTRACT FROM AUTHOR]

Simple Summary: Serum concentrations of feline pancreatic lipase immunoreactivity (fPLI), feline trypsin-like immunoreactivity (fTLI), and cobalamin are commonly used for the diagnostic investigation of cats with gastrointestinal signs. No information on these parameters in healthy cats less than 1 year of age exists. We aimed to evaluate serum concentrations of fPLI, fTLI, and cobalamin in healthy cats at different time-points during their first 12 months of life. Fourteen healthy 2-month-old kittens were included. Blood was collected at 2, 3, 4, 6, and 12 months of age, and serum concentrations of fPLI, fTLI, and cobalamin were measured. Serum fPLI and fTLI concentrations did not show any statistically or clinically significant differences in young kittens. In contrast, serum cobalamin concentrations were commonly below the reference interval in kittens. Serum fPLI and fTLI concentrations are not practically affected by age in kittens as young as 2 months of age and could be used for the investigation of pancreatic diseases. Serum concentrations of feline pancreatic lipase immunoreactivity (fPLI), feline trypsin-like immunoreactivity (fTLI), and cobalamin are commonly used for the diagnostic investigation of cats with gastrointestinal signs. No information on these parameters in healthy cats less than 1 year of age exists. We aimed to evaluate serum concentrations of fPLI, fTLI, and cobalamin in healthy cats at different time-points during their first 12 months of life. Fourteen healthy 2-month-old kittens were included. Blood was collected at 2, 3, 4, 6, and 12 months of age, and serum concentrations of fPLI, fTLI, and cobalamin were measured. While there was a statistically significant difference in serum fPLI concentrations over time, there was no statistically significant difference between individual time-points. There was no significant difference in serum fTLI concentrations over time. Serum cobalamin concentrations were below the reference interval in 3/13 cats at 2 months of age and were significantly lower by 3 months, when 13/14 had hypocobalaminemia. By 12 months, serum cobalamin had significantly increased, yet 4/12 cats still had hypocobalaminemia. Serum fPLI and fTLI concentrations did not show any statistically or clinically significant differences in young kittens. In contrast, serum cobalamin concentrations were commonly below the reference interval in kittens. Serum fPLI and fTLI concentrations are not practically affected by age in kittens as young as 2 months of age and could be used for the investigation of pancreatic diseases. [ABSTRACT FROM AUTHOR]

Antibiotics cause gut dysbiosis and bile acid dysmetabolism in dogs. The effect of fecal microbiota transplantation (FMT) on microbiome and metabolome recovery is unknown. This prospective, randomized, placebo-controlled study included sixteen healthy purpose-bred dogs. All dogs received tylosin 20 mg/kg PO once daily (days 1–7) and were randomly assigned to either receive one FMT via enema (day 8), daily oral FMT capsules (days 8–21), or daily placebo capsules (days 8–21). Fecal samples were frozen at regular intervals until day 42. Quantitative PCR for 8 bacterial taxa was performed to calculate the fecal dysbiosis index (FDI) and fecal concentrations of unconjugated bile acids (UBA) were measured using gas chromatography-mass spectrometry. Tylosin altered the abundance of most evaluated bacteria and induced a significant decrease in secondary bile acid concentrations at day 7 in all dogs. However, most parameters returned to their baseline by day 14 in all dogs. In conclusion, tylosin markedly impacted fecal microbiota and bile acid concentrations, although return to baseline values was quick after the antibiotic was discontinued. Overall, FMT did not accelerate recovery of measured parameters. Further studies are warranted to confirm the value of FMT in accelerating microbiota recovery in antibiotic-associated dysbiosis in dogs. [ABSTRACT FROM AUTHOR]

This document is a comment on a study that investigated the potential association between domestic cat hepadnavirus (DCH) infection and lymphoma in cats. The authors of the comment highlight that while there have been studies reporting an increased risk of non-Hodgkin's lymphoma in humans infected with hepatitis B virus (HBV), there is no evidence of a similar risk in chronic hepadnavirus infection in other species. They also point out limitations in the study design used by the original authors, which may affect the interpretation of the results. The comment concludes by stating that the presented data does not support a direct relationship between DCH infection and feline lymphoma. [Extracted from the article]

Canine fiber responsive diarrhea is a form of chronic colitis that improves clinically after adding fiber to the diet. In the present study, we investigated the effect of a combination of a high-fiber, highly digestible, hypoallergenic diet with a probiotic mixture in 30 dogs with chronic colitis that were unresponsive to various dietary and/or pharmacological interventions. Fecal scores, canine chronic enteropathy clinical activity index (CCECAI) scores, the dysbiosis index (DI), and histologic images of colonic biopsies were evaluated. At baseline (day 0; T0) and after 30 days of treatment (T1), all variables evaluated in our patients (i.e., fecal and CCECAI scores and histopathology) improved significantly at T1, with the exception of DI. However, there was a numerical shift from a state of dysbiosis to one of normobiosis. The combination of the diet and the probiotic used in the present study induced the resolution of clinical signs in a mean of 8.5 days (maximum 15 days) and did not necessitate any other treatments or the further addition of alimentary fiber. [ABSTRACT FROM AUTHOR]

This document is a reply to a comment made by Piewbang et al. regarding the presence of domestic cat hepadnavirus in lymphoma tissues. The authors express gratitude for the additional data provided by Piewbang et al. and acknowledge that Veterinary Quarterly, the original publisher of the article, no longer accepts Letters to the Editor. The authors declare no conflicts of interest. [Extracted from the article]

Simple Summary: This study investigated the impact of antibiotic treatment οn the serum and fecal metabolome (the collection of all small molecules produced by the gut bacteria and the host) of young cats. Thirty 2-month-old cats with an upper respiratory tract infection were treated with either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days. In addition, another 15 control cats that did not receive antibiotics were included. Blood was collected on days 0 (before treatment), 20/28 (last day of treatment), and 300 (10 months after the end of treatment), while feces were collected on days 0, 20/28, 60, 120, and 300. Seven serum and fecal metabolites differed between cats treated with antibiotics and control cats at the end of treatment period. Ten months after treatment, no metabolites differed from healthy cats, suggesting that amoxicillin/clavulanic acid or doxycycline treatment only temporarily affects the abundance of the serum and fecal metabolome. The long-term impact of antibiotics on the serum and fecal metabolome of kittens has not yet been investigated. Therefore, the objective of this study was to evaluate the serum and fecal metabolome of kittens with an upper respiratory tract infection (URTI) before, during, and after antibiotic treatment and compare it with that of healthy control cats. Thirty 2-month-old cats with a URTI were randomly assigned to receive either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days, and 15 cats of similar age were enrolled as controls. Fecal samples were collected on days 0, 20/28, 60, 120, and 300, while serum was collected on days 0, 20/28, and 300. Untargeted and targeted metabolomic analyses were performed on both serum and fecal samples. Seven metabolites differed significantly in antibiotic-treated cats compared to controls on day 20/28, with two differing on day 60, and two on day 120. Alterations in the pattern of serum amino acids, antioxidants, purines, and pyrimidines, as well as fecal bile acids, sterols, and fatty acids, were observed in antibiotic-treated groups that were not observed in control cats. However, the alterations caused by either amoxicillin/clavulanic acid or doxycycline of the fecal and serum metabolome were only temporary and were resolved by 10 months after their withdrawal. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of treatment of dogs with steroid-responsive enteropathy (a form of chronic diarrhea that responds to treatment with a corticosteroid) on the intestinal microbiome (the collection of all microorganisms in the GI tract) and metabolome (the collection of all small molecules produced by the microbiome or the host) was investigated in this study. Dogs receiving standard treatment were evaluated before (week 0), during (week 3), and at the end of treatment (week 8), as well as 1 year later, in comparison to healthy control dogs. None of the dogs had clinically relevant signs of disease at the end of treatment. While both the microbiome and the metabolome normalized to some degree after treatment, some key bacteria and many molecules remained different, suggesting that certain abnormalities persisted. However, 1 year after treatment, both the microbiome and the metabolome were no longer different from healthy dogs, suggesting that intestinal recovery from chronic steroid-responsive enteropathy takes longer than resolution of clinical signs would suggest. The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fecal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospectively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seventy-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species were evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen metabolites were no longer different from healthy controls. [ABSTRACT FROM AUTHOR]

Simple Summary: Antimicrobials reduced the diversity and altered the bacterial community composition of the fecal microbiome of horses. Horses that develop antimicrobial-associated diarrhea (AAD) show greater derangements in their bacterial community composition compared to antibiotic (ABX) and non-antibiotic (CON) control horses. Horses with AAD have altered metabolic profiles compared to ABX and CON horses. Diarrhea is an adverse effect of antimicrobial therapy in horses. This matched, case-controlled study compared the fecal microbiome and metabolome of horses on antibiotics that developed diarrhea (AAD, n = 17) to those that did not develop diarrhea (ABX, n = 15) and to a control population not exposed to antibiotics (CON, n = 31). Fecal samples were collected from horses that were matched for diet and antimicrobial agent (including dose, route, and duration of therapy). Illumina sequencing of 16S rRNA genes was performed, and QIIME 2.0 was used to generate alpha and beta diversity metrics. Untargeted metabolomics using GC-MS platforms was performed and analyzed using Metaboanalyst 5.0. Microbiome composition was significantly different in AAD compared to CON (ANOSIM, R = 0.568, p = 0.001) but not to ABX (ANOSIM, R = 0.121, p = 0.0012). AAD and ABX horses had significantly decreased richness and evenness compared to CON horses (p < 0.05). Horses on antimicrobials (AAD and ABX) had significant changes in 14 phyla compared to CON horses. Only Verrucomicrobia distinguished AAD from ABX and CON horses (q = 0.0005). Metabolite profiles of horses with AAD clustered separately from ABX and CON horses. Seven metabolites were found to be significantly different between groups (p < 0.05): L-tyrosine, kynurenic acid, xanthurenic acid, 5-hydroxyindole-3-acetic acid, docosahexaenoic acid ethyl ester, daidzein, and N-acetyltyramine. Metabolite profiles of horses on antimicrobials, especially those with AAD, are altered compared to CON horses. [ABSTRACT FROM AUTHOR]