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Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

ABSTRACT: Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7521520 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

Zhang Lijing L Zhou Wen W Zhan Libin L Hou Shenglin S Zhao Chunyan C Bi Tingting T Lu Xiaoguang X

Aging 20200912 17

Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional e ...[more]

PMID: 32920548

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Project description:PurposeThe purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.MethodsThirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.ResultsG__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.ConclusionsG__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.

Project description:Fecal microbiota transplantation (FMT) documented transplanting a donor fecal sample to a receipt individual for a desired physiologic effect. However, whether the gut microbiota construction, intestinal maturation, and behavioral plasticity are modulated by FMT during the early life of broilers is waiting for verification. To evaluate the role of transfer of fecal microbiota from aged broilers donor (BD) to another individual, 96 birds were equally divided into a check (CK, control) group and a broiler recipient (BR) group. FMT was conducted daily from 5 to 12 days of age to determine the future impact on body weight, behavior, intestinal development, and gut microbiota. Results indicated that fearfulness in the CK group was higher than the BR group in both the behavioral tests (p < 0.05). The muscularis mucosa, thickness of muscle layer, and thickness of serous membrane layer in the BR group were higher compared with those of the CK group in the jejunum (p < 0.05). In the gut microbiota, Shannon diversity showed no difference, while beta diversity presented a difference in principal coordination analysis (PCoA) between the CK and BR groups. At the phylum level, the relative abundance of Lentisphaerae in the CK group was lower than the BR (p = 0.052) and BD (p = 0.054) groups. The relative abundance of Tenericutes in the BD group was higher than that in the CK and BR groups (p < 0.05). At the genus level, Megamonas in the CK group was higher than the BR (p = 0.06) and BD (p < 0.05) groups. In the BR group, the functional capabilities of microbial communities analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were increased in the glutamatergic synapse and N-glycan biosynthesis pathways in comparison with the CK and BD groups (p < 0.05). Some characteristics of gut microbiota in the donor chickens could be transferred to recipient chickens by FMT. In conclusion, exogenous FMT as a probiotic-like administration might be an efficient way to improve the physiology and behavior of chickens. Notably, the role of microbiota for various individuals and periods remains undefined, and the mechanism of microbiota on behaviors still needs further investigation.

Project description:BackgroundModifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored.AimThis study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM.MethodsIn this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878).ResultsA noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota.Clinical parametersA significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05).Gut microbiomeTreatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group.Oral microbiotaAfter Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed.Ocular surface microbiotaPost-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota.ConclusionCana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

Dataset Information

Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

Publications

Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

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