Background The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn’s disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. Results We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens ), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens , was associated with diet-induced remission in human pediatric Crohn’s disease. Conclusions These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn’s disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets. Electronic supplementary material The online version of this article (10.1186/s40168-019-0740-4) contains supplementary material, which is available to authorized users.
Forty-four cats diagnosed with moderate to severe cholangitis at necropsy are described. The population comprised 0.86% of all feline necropsies performed during the 22-year study period. Liver specimens were classified as acute neutrophilic cholangitis (ANC), chronic neutrophilic cholangitis (CNC), lymphocytic cholangitis (LC) or chronic cholangitis associated with liver fluke infestation (CC) based on the World Small Animal Veterinary Association (WSAVA) classification scheme. ANC (seven) and CNC (33) comprised the majority of cases. In contrast to previous descriptions, overlap was seen in clinical findings between ANC and CNC subtypes. Results suggest that liver enzyme activity may not predict degree of inflammation. Severity of inflammation varied between liver sections in individual cats, underscoring the need to obtain biopsy samples from multiple sites. Inflammatory bowel disease (50%), pancreatitis (60%), or both (32%) commonly accompanied cholagitis. We conclude that cholangitis is not a common cause of feline mortality. Most cats that succumb to cholangitis have ANC or CNC, and concurrent disease contributes to death in many.
Medical records of 16 cats diagnosed with exocrine pancreatic insufficiency (EPI) were reviewed. The diagnosis was confirmed with either a serum feline trypsin-like immunoreactivity (fTLI) concentration
The goals of this study were to determine the historical, physical examination, and clinicopathologic findings in dogs with suppurative, nonseptic polyarthropathy and to identify concurrent disorders associated with this syndrome. Medical records of 52 dogs with cytologic evidence of suppurative inflammation in two or more joints were examined retrospectively. Age of dogs was 4.8 years (median, range: 0.5-12 years). There was no clear breed or sex predilection, but most were large-breed dogs (body weight > or = 20 kg [44.4 lbs] in 40/52). Body temperature was 103.0 degrees F (39.4 degrees C) (median, range: 100.0-105.9 degrees F), with 29 of 52 dogs having a body temperature > or = 103 degrees F (39.4 degrees C). Lameness was identified in 42 of 52 dogs. Erosive changes were found in only 1 of 37 dogs that had radiography performed. A clear underlying disease process was not identified in 34 of 52 dogs. Seven dogs had evidence of infectious or inflammatory processes at extra-articular sites; 4 dogs were diagnosed with systemic lupus erythematosus (SLE); 2 dogs had gastrointestinal disease; 2 dogs had been vaccinated within 1 month before onset of polyarthritis; 1 dog had cancer; 1 dog had polyarthritis and meningitis; and 1 dog had erosive polyarthritis. Of the 44 dogs tested, 25 had antibodies to Borrelia burgdorferi, detected by an ELISA assay, which was significantly greater than the general hospital population (P = .007). Antibodies against Rickettsia rickettsiae and Ehrlichia canis were not definitively identified in the sera of any dog tested in this study (45 and 44 dogs, respectively). We conclude that an underlying disease process is not identified in most cases of suppurative polyarthropathy in dogs and that intestinal disease, neoplasia, and SLE are uncommon causes of polyarthritis. While seropositivity against the causative agent of Lyme disease was common and possibly a cause of polyarthritis in some dogs of our study, evidence of other vector-borne infection was not identified.
Transnasal balloon-expandable metallic stent placement may represent a rapid, safe, noninvasive, and effective treatment in animals with nasopharyngeal stenosis. If the stenosis is extremely caudal in the nasopharynx, serial balloon dilatation might be considered prior to stent placement. A covered stent should be considered initially if the stenosis is completely closed.
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