Submitted by: Patricia Shea, DVM
Sci Rep 2019;9:4822. DOI: 10.1038/s41598-019-41195-0
Diabetic cats have decreased gut microbial diversity and a lack of butyrate producing bacteria.
Kieler IN, Osto, M, et al.
Information regarding the possible or actual role of the gastrointestinal microbiome in the etiology and sequelae of a variety of diseases and syndromes in both human and nonhuman animals is now appearing almost daily in the scientific and popular media. Type 2 (“adult onset”) diabetes mellitus (T2DM) in humans is one such disease; there is mounting evidence that gastrointestinal dysbiosis is present in these individuals. Specifically, there are decreased numbers of bacteria producing butyrate, a short-chain fatty acid (SCFA), in T2DM patients compared to controls. The SCFAs: acetate, butyrate, and propionate, are produced through fermentation of complex polysaccharides by microbes in the large intestine; these substances help facilitate glucose and energy metabolism and support local immune function. Butyrate in particular supplies energy for the cells in the colonic mucosa, and may increase insulin sensitivity and energy expenditure. Decreased butyrate levels may be significantly associated with the development of insulin resistance.
Feline diabetes mellitus (FDM) is considered to be an animal model of human T2DM. As in their human counterparts, cats with FDM are middle-aged to elderly, frequently overweight to obese, and have impaired insulin secretion, peripheral insulin resistance, loss of beta islet cells, and development of amyloid deposits in the insulin-producing pancreatic islets. The current study involved genetic sequencing of 121 microbial DNA samples from feces of 82 privately owned cats from Denmark and Switzerland and consisted of two parts: (1) a cross-sectional study aimed at identifying differences between the gastrointestinal microbiomes of diabetic (group DM), healthy lean (LN; BCS 4-5/9), and healthy overweight/obese cats (OB; BCS 7-9/9), and (2) an interventional study to determine if changes could be made to the gastrointestinal microbiome of a subset of these cats by feeding a high-protein/low-carbohydrate commercial diet specifically formulated for feline diabetics.
After extraction from the fecal samples, the microbial DNA concentrations were estimated, then amplified multiple times by PCR. The fecal bacterial microbiota composition was determined by next-generation sequencing of 16S ribosomal RNA.
Of the 121 fecal samples, those from 62 of the cats (23 DM, 15 OB, and 24 LN) had sufficient nucleic acid reads to be included in a statistical analysis. Most of the cats were indoor only, although 4 DM, 2 LN, and 2 OB had limited outdoor access. All cats in the study were over 6 years of age, had not received any antibiotics within the four months previous to recruitment, and also had not received any probiotics or prebiotics within two weeks of inclusion.
All but one (newly diagnosed) of the DM cats were receiving insulin of some kind. In the genetic sequencing portion of the study, the DM cats were found to have a less diverse gastrointestinal microbiome than the LN or OB groups. Moreover, hemoglobin and packed cell volume correlated positively with the richness of the gastrointestinal microbiome, while serum bile acid levels, serum fructosamine, and serum glucose levels correlated negatively with gastrointestinal microbiome richness. Compared to the LN and OB cats, the DM cats had decreased proportions of Bacteroidetes, Bacteroida, Bacteroidales, Prevotellaceae, and Prevotella. Breed, sex, and age of the subjects were not found to influence the composition of the microbial communities.
Butyrate-producing bacterial genera were decreased in the DM group compared to the LN group. Numbers of Enterobacteriaceae family bacteria, which are associated with systemic low-grade inflammation, correlated positively with serum fructosamine levels, while Prevotellaceae family numbers correlated negatively with serum fructosamine levels. Some members of the Prevotellaceae are known to be associated with improved glucose tolerance in mice.
The reduced diversity of the gastrointestinal microbiome and a tendency to harbor more pro-inflammatory microbiota as well as substantial decreases in butyrate-producing bacteria observed in diabetic cats parallel findings in humans with T2DM. These changes were not found in the healthy OB group, so it is likely that body composition alone does not predispose to the development of FDM.
In the second, interventional portion of the study, a subset of the cats from Denmark only (10 DM, 11 LN, and 13 OB) were fed a commercial high-protein, low-carbohydrate dry diet (Royal Canin Diabetic Feline) for four weeks, and fecal samples were again collected for analysis of microbial genetic material. The dietary intervention did not improve the diversity or composition of the gastrointestinal microbiome in the DM cats compared to that in the LN or OB cats. Although the small sample size and relatively short length of treatment involved in this portion of the study could have contributed to the lack of significant change observed, it is possible that probiotic supplementation, including butyrate-producing bacteria, or fecal transplantation, could be important in the future treatment of diabetic cats. Another potential avenue of future research could be to evaluate the influence of a canned high-protein diet designed for diabetic cats on the gastrointestinal microbiome of these patients and healthy controls.
J Vet Intern Med. 2019;1–10. DOI: 10.1111/jvim.15672
Cardiac cachexia in cats with congestive heart failure: Prevalence and clinical, laboratory, and survival findings.
Santiago SL, Freeman LM, Rush JE.
Cardiomyopathies and congestive heart failure (CHF) pursuant to these cardiomyopathies are relatively common in cats. The presence of cachexia, a complex condition involving both muscle wasting and weight loss, is well known in both people and dogs with CHF. Cachexia can also occur in association with other diseases, such as chronic kidney disease and neoplasia. Cachexia is a disease-related phenomenon, while sarcopenia refers to muscle wasting associated with aging in the absence of intercurrent disease.
The purpose of this retrospective study of the medical records of 125 cats with CHF was to determine if cachexia was also present in cats with CHF and to learn about its potential association with clinical signs, laboratory findings, and survival time in cats with CHF. Prior to beginning the study, the investigators had to determine the criteria for identification of cachexia that they would use in analyzing the records of the feline patients. In humans, at least 11 definitions of cachexia are used. Seven different definitions of cachexia were initially used to identify cardiac cachexia in the cats’ medical records.
Weight loss is one of the criteria commonly used to identify cardiac cachexia in people, but loss of muscle mass is now considered the most important factor in promoting the negative effects of cachexia. Humans in CHF accompanied by muscle loss, with or without weight loss, have more functional deficits and decreased quality of life compared to those who have experienced weight loss only. The investigators’ working hypothesis was that muscle condition scoring was most likely to identify more cats with cardiac cachexia than other criteria.
The seven definitions of cachexia used to evaluate the records of the 125 cats with CHF were as follows:
- Weight loss of at least 5% in the 12 months following CHF diagnosis and 3 of the following criteria at the time of diagnosis: decreased muscle strength, fatigue, anorexia, low fat-free mass index, or biochemical abnormalities (anemia or hypoalbuminemia);
- At least one prescription for appetite stimulation pharmaceuticals such as mirtazapine or cyproheptadine;
- 5% or more weight loss after CHF diagnosis;
- More than 5% weight loss in the 6 months prior to CHF diagnosis;
- Unintended loss of 5% or more of body weight in the 6-12 months prior to CHF diagnosis;
- Low body condition score (BCS; <4/9) at the time of CHF diagnosis;
- Muscle loss based on muscle condition score (MCS) at the time of CHF diagnosis.
Data for all 125 cats were only available for criteria (6) and (7). Only 15/125 (12.0%) met criterion (6), while 52/125 (41.6%) met criterion (7). Ultimately, given that all 125 cats had MCS available in their records, that muscle is the body compartment most adversely affected in cachexia, and that MCS reflects loss of muscle mass only, unlike criteria (1), (3), (4), (5) and (6), further analysis of the records used MCS only (criterion 7) to categorize cats with or without cachexia.
Study cats diagnosed with CHF ranged in age from 1.2-19.6 years (median age 10.3 years). There were 89 neutered males and 36 spayed females. Most of the cats (n = 101) were domestic shorthair or domestic longhair; the rest represented a variety of breeds. Hypertrophic cardiomyopathy was present in 107 cats; dilated cardiomyopathy in 8, unclassified or restrictive cardiomyopathy in 8, and 2 had arrhythmogenic right ventricular cardiomyopathy.
The cats with cachexia were more likely to have pleural effusion than cats without cachexia. Hematocrit and hemoglobin concentrations in cachectic cats were lower than in non-cachectic cats. Cats with cachexia were older, and had higher BUN concentrations and higher BUN/creatinine ratios, but not higher creatinine. Significantly higher neutrophil concentrations, lower BCS, and lower body weights were also found in the cachectic cats. It is likely that some of the older cats with cachexia had concurrent sarcopenia. Significantly shorter survival times based on all-cause mortality were found in the cats with cachexia based on MCS; however, this only demonstrates association and not causation. Nonetheless, this association should prompt the clinician to identify, and if possible, treat cachexia in cats with CHF.
Although cats with other concurrent diseases that could be associated with muscle loss and decrease in body weight, such as neoplasia, chronic kidney disease, diabetes mellitus or unregulated hyperthyroidism, were excluded from the study, sarcopenia and/or occult disease could have coexisted with cachexia in some of the patients included in the study. In order to further evaluate the prevalence, role and impact of cachexia in cats with CHF, and its potential relationship with echocardiographic findings, the authors recommend that echocardiographic measurements be included in future studies of larger groups of cats with CHF.