scholarly journals Effects of Short Chain Fatty Acids (SCFAs) Modulation on Potentially Diarrhea Causing Pathogens in Yaks Through Metagenomics Sequencing

2020 ◽  
Author(s):  
Kun Li ◽  
Zhibo Zeng ◽  
Juanjuan Liu ◽  
Lulu Pei ◽  
Yaping Wang ◽  
...  

Abstract Yaks are of great importance on the plateau; however, an emerging endemic diarrheal disease during the last few years is posing a great threat to the health of these animals. Yaks have special gut microbiotal community and short-chain fatty acids (SCFAs) which are not only the principle nutrient substrates of intestinal epithelial cells but can also regulate the epithelial barrier. Until now, metagenomics sequencing has not been reported in diarrheal yaks. A scarce information is available regarding the levels of fecal SCFAs and diarrhea in yaks. The purpose of our study was to identify the potential pathogens that cause the emerging diarrhea and also to explore the potential relationship of short-chain fatty acids in this issue. We estimated diarrhea rate in yaks after collecting the equal number of fecal samples from affected animals. Metagenomics sequencing and quantitative analysis of SCFAs were performed which revealed 15-25% and 5-10% prevalence in diarrheal yak’s calves and adults yaks respectively. Significant difference was observed in GC contents (44.69%~46.08% vs 46.12%~46.38%) under two reference groups (p<0.05). Violin box plot also showed the higher degree of dispersion in gene abundance distribution of diarrhea yaks, while genes of normal yaks were relatively gathered. We found 366163 significant differential abundance genes in diarrheal yaks, with 141305 up-regulated and 224858 down-regulated genes as compared with normal yaks via DESeq analysis. Metagenomic binning analysis indicated the higher significant of bin 33 (Bacteroidales) (p<0.05) in diarrheal animals, while bin 10 (p<0.0001), bin 30 (Clostridiales) (p<0.05), bin 51 (Lactobacillales) (p<0.05), bin 8 (Lachnospiraceae) (p<0.05) and bin 47 (Bacteria) (p<0.05) were obviously higher in normal animals. At different levels, an obviously difference in Phylum, Class, Oder, Family, Genus and Species was noticed as 4, 8, 8, 16, 17 and 30 respectively. Compared with healthy yaks, Acetic acid (p<0.01), Propionic acid (p<0.01), Butyric acid (p<0.01), Isobutyric acid, Isovaleric acid (p<0.05) and Caproic acid (p<0.01) were all observed obviously at lower rate in diarrheal yaks. In conclusion, besides the increased pathogens level of Staphylococcus aureus, Babesia ovata, Anaplasma phagocytophilum, Bacteroides fluxus, viruses, Klebsiella pneumonia, and inflammation-related bacteria; the decreased of SCFAs caused by the imbalance of intestinal microbiota may potentially leads to emergence of diarrhea in yaks.

2015 ◽  
Vol 17 (5) ◽  
pp. 662-671 ◽  
Author(s):  
Caleb J. Kelly ◽  
Leon Zheng ◽  
Eric L. Campbell ◽  
Bejan Saeedi ◽  
Carsten C. Scholz ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Justine Huart ◽  
Arianna Cirillo ◽  
Annie Saint-Remy ◽  
Jean-Marie Krzesinski ◽  
Pascal De Tullio ◽  
...  

Abstract Background and Aims Gut microbiota (GM) has been involved in the pathophysiology of hypertension (HT), possibly via its role in the production of short chain fatty acids (SCFAs) from diet carbohydrate fermentation. The absence of a significant drop in night-time BP (also known as the non-dipping BP profile) measured by 24-hour ambulatory BP monitoring (24h-ABPM) has been associated with poor renal and cardiovascular outcomes, independently of HT. The putative link between GM-derived metabolites and BP dipping status is still unknown. Method We investigated a cohort of male volunteers who were prospectively recruited and subjected to 24h-ABPM, stool sample collection and a medical questionnaire. A patient was categorized as non-dipper if the ratio between night and day systolic BP was &gt;0.9. The patients were categorized in two groups, i.e. NT or HT, on the basis of the European Society of Hypertension criteria. Metabolomics analyses were conducted using Nuclear Magnetic Resonance. Fecal concentrations of acetate, butyrate and propionate were obtained by integrating the signals at 1.93 ppm, 1.56 ppm and 1.05 ppm, respectively. Mann-Whitney test and Chi-square test were used to compare continuous and categorical variables, respectively. Results Our 44-case cohort included 13 non-dippers (29.6%) and 31 dippers, with 35 HT (79.4%) and 9 NT patients. Ten non-dippers (28.6%) and 25 dippers were HT. Nineteen HT patients were under anti-hypertensive medications (43.1%), including 7 non-dippers and 12 dippers. The mean age and body mass index (BMI) of the cohort were 50.8±9.5 years and 26.3±3.5 kg/m², respectively. No significant difference in age, BMI, smoking habits, alcohol consumption, familial HT, personal history of diabetes, cardiovascular or gastro-intestinal disorders was observed between dippers and non-dippers. The relative quantification of fecal SCFAs showed higher amounts of acetate, butyrate and propionate in the stools of non-dippers versus dippers (p=0.0252, p=0.0468, and p=0.0496, respectively; n=44 in toto) (Figure 1A). Similarly, the fecal amounts of acetate, butyrate and propionate were higher in non-dippers versus dippers in patients without anti-hypertensive medications (p=0.0414, p=0.0108, and p=0.0602, respectively; n=25 in toto) (Figure 1B). When focusing only on HT patients without any anti-hypertensive medications, a not significant trend for higher amounts of the 3 main SCFAs was still found in the stools of non-dippers versus dippers (p=0.0556; n=16 in toto). Conclusion Our pilot study highlights a putative link between GM-derived SCFAs and the BP dipping status, despite the BP status itself or the anti-hypertensive medications. No significant confounding factors were found between dippers and non-dippers in our cohort. The non-dipping BP profile is thought to reflect the disruption of the circadian BP rhythm. A circadian misalignment between peripheral and central clocks has also been described in the GM of jetlagged animals and patients, which may in turn perturb the rhythmic secretion of metabolites. One may thus speculate that the non-dipping BP profile may be linked to an altered homeostasis of GM-derived SCFAs. Although confirmatory data in larger cohorts are required, our original observations unravel innovative pathophysiological pathways in the field of the circadian regulation of BP levels.


2020 ◽  
Author(s):  
Deborah H. Luzader ◽  
Jibraan A. Fawad ◽  
Thomas J. Moutinho ◽  
Paul G. Mitchell ◽  
Kathleen Brown-Steinke ◽  
...  

ABSTRACTBackground and aimsThe circadian clock orchestrates ~24-hour oscillations of gastrointestinal (GI) epithelial structure and function that drive diurnal rhythms in the composition, localization, and metabolism of gut microbiota. Here, we use experimental and computational approaches in enteroids to reveal reciprocal effects of microbial metabolites on intestinal epithelial timekeeping by an epigenetic mechanism.MethodsWe cultured 3D PER2∷LUCIFERASE and Bmal1-ELuciferase jejunal enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota. Circadian oscillations of bioluminescent PER2 and Bmal1 were measured in enteroids cultured in the presence or absence of individual ASF supernatants. Separately, we applied machine learning to ASF metabolic profiles to identify phase-shifting metabolites.ResultsFiltrates from 3 of 7 ASF species (ASF360 Lactobacillus intestinalis, ASF361 Ligilactobacillus murinus, ASF502 Clostridium spp.) induced minimal alterations in circadian rhythms, whereas 4 ASF species (ASF356 Clostridium spp., ASF492 Eubacterium plexicaudatum, ASF500 Pseudoflavonifactor spp., ASF519 Parabacteroides goldsteinii) induced profound, concentration-dependent phase delays. Random forest classification identified short chain fatty acids (SCFA: butyrate, propionate, acetate, and isovalerate) production as a discriminating feature of “shifters”, i.e., ASF taxa whose metabolites induce phase delay. Experiments with SCFAs confirmed machine learning predictions, with a median phase delay of 6.2 hours. Pharmacological or botanical HDAC inhibitors generated similar phase delays. Further, mithramycin A, an inhibitor of HDAC inhibition, abrogated SCFA-induced phase delays by 20% (P<0.05). Key findings were reproducible in human Bmal1-luciferase enteroids.ConclusionsGut microbe-generated SCFAs entrain intestinal epithelial circadian rhythms, in part, by an HDACi-dependent mechanism, with critical implications for understanding microbial and circadian network regulation of intestinal epithelial homeostasis.


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