Rotundic Acid Protects against Metabolic Disturbance and Improves Gut Microbiota in Type 2 Diabetes Rats

Rotundic acid (RA) is a major triterpene constituent in the barks of Ilex rotunda Thunb, which have been widely used to make herbal tea for health care in southern China. RA has a variety of bioactivities such as anti-inflammation and lipid-lowering effect. However, little is known about the effects and mechanisms of RA on metabolic disturbance in type 2 diabetes (T2D) and its effect on gut microbiota. A T2D rat model induced by high fat diet (HFD) feeding and low-dose streptozotocin (STZ) injection was employed and RA showed multipronged effects on T2D and its complications, including improving glucolipid metabolism, lowering blood pressure, protecting against cardiovascular and hepatorenal injuries, and alleviating oxidative stress and inflammation. Furthermore, 16s rRNA gene sequencing was carried out on an Illumina HiSeq 2500 platform and RA treatment could restore the gut microbial dysbiosis in T2D rats to a certain extent. RA treatment significantly enhanced the richness and diversity of gut microbiota. At the genus level, beneficial or commensal bacteria Prevotella, Ruminococcus, Leuconostoc and Streptococcus were significantly increased by RA treatment, while RA-treated rats had a lower abundance of opportunistic pathogen Klebsiella and Proteus. Spearman’s correlation analysis showed that the abundances of these bacteria were strongly correlated with various biochemical parameters, suggesting that the improvement of gut microbiota might help to prevent or attenuate T2D and its complication. In conclusion, our findings support RA as a nutraceutical agent or plant foods rich in this compound might be helpful for the alleviation of T2D and its complications through improving gut microbiota.

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Alteration of Gut Microbiota in type 2 Diabetes Complicated with Cholelithiasis Patients

10.21203/rs.3.rs-52504/v1 ◽

2020 ◽

Author(s):

Jiajia Chen ◽

Linlin Yan ◽

Xingfan Ma ◽

Ping Yuan ◽

Fan Zhao ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

Elevated Serum ◽

Serum Triglyceride ◽

16S Rrna Gene Sequencing ◽

Epidemiological Studies ◽

Rrna Gene ◽

Microbial Composition ◽

Diabetes Patients

Abstract Background: Epidemiological studies showed that diabetes patients are more prone to developing cholelithiasis. Although composition of gut microbiota in type 2 diabetes or cholelithiasis have been studied respectively, the underlying role of gut microbiota in developing from diabetes to cholelithiasis remains unclear. By 16S rRNA gene sequencing, the gut microbial composition of 33 healthy subjects, 53 type 2 diabetes, 31 cholelithiasis and 32 type 2 diabetes complicated with cholelithiasis patients were studied. Results: Microbial diversity significantly decreased in type 2 diabetes complicated with cholelithiasis patients. In type 2 diabetes patients, phylum Proteobacteria class Gammaproteobacteria and order Lactobacillales were significantly increased. In cholelithiasis patients, phylum Bacteroidetes, class Bacteroidia order Bacteroidales family Bacteroidaceae and genus Bacteroides were significantly increased. There were also significant increases of phylum Proteobacteria, class Gammaproteobacteria order Lactobacillales family Lactobacillaceae and genus Lactobacillus in type 2 diabetes complicated with cholelithiasis patients accompanied by elevated serum triglyceride and total bile acids. Conclusions: The results show similar but more intricate gut microbiota dysbiosis in type 2 diabetes complicated with cholelithiasis compared with type 2 diabetes, which might partially explain the mechanism of type 2 diabetes as the risk factor of cholelithiasis from the perspective of gut microbiota.

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Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents

Journal of Diabetes Research ◽

10.1155/2020/7253978 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Babiker Saad Almugadam ◽

Yinhui Liu ◽

Shen-min Chen ◽

Chun-hao Wang ◽

Chen-yi Shao ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

Bacterial Flora ◽

Control Group ◽

Rrna Gene ◽

Antidiabetic Agents ◽

Antidiabetic Therapy ◽

Healthy Control ◽

Substantial Decline

Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8 ) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.

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Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy

Scientific Reports ◽

10.1038/s41598-021-82538-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Taraprasad Das ◽

Rajagopalaboopathi Jayasudha ◽

SamaKalyana Chakravarthy ◽

Gumpili Sai Prashanthi ◽

Archana Bhargava ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Retinopathy ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

R Software ◽

Bacterial Microbiome ◽

Rrna Gene Sequencing

AbstractGut bacterial microbiome dysbiosis in type 2 Diabetes Mellitus (T2DM) has been reported, but such an association with Diabetic Retinopathy (DR) is not known. We explored possible link between gut bacterial microbiome dysbiosis and DR. Using fecal samples of healthy controls (HC) and people with T2DM with/without DR, gut bacterial communities were analysed using 16S rRNA gene sequencing and data analysed using QIIME and R software. Dysbiosis in the gut microbiomes, at phyla and genera level, was observed in people with T2DM and DR compared to HC. People with DR exhibited greater discrimination from HC. Microbiomes of people with T2DM and DR were also significantly different. Both DM and DR microbiomes showed a decrease in anti-inflammatory, probiotic and other bacteria that could be pathogenic, compared to HC, and the observed change was more pronounced in people with DR. This is the first report demonstrating dysbiosis in the gut microbiome (alteration in the diversity and abundance at the phyla and genera level) in people with DR compared to HC. Such studies would help in developing novel and targeted therapies to improve treatment of DR.

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Metagenomic Insights into the Degradation of Resistant Starch by Human Gut Microbiota

Applied and Environmental Microbiology ◽

10.1128/aem.01562-18 ◽

2018 ◽

Vol 84 (23) ◽

Cited By ~ 18

Author(s):

Marius Vital ◽

Adina Howe ◽

Nathalie Bergeron ◽

Ronald M. Krauss ◽

Janet K. Jansson ◽

...

Keyword(s):

Gut Microbiota ◽

Resistant Starch ◽

Treatment Strategies ◽

16S Rrna Gene Sequencing ◽

Noncommunicable Diseases ◽

Rrna Gene ◽

Functional Responses ◽

Content Type ◽

Coa Transferase

ABSTRACTSeveral studies monitoring alterations in the community structure upon resistant starch (RS) interventions are available, although comprehensive function-based analyses are lacking. Recently, a multiomics approach based on 16S rRNA gene sequencing, metaproteomics, and metabolomics on fecal samples from individuals subjected to high and low doses of type 2 RS (RS2; 48 g and 3 g/2,500 kcal, respectively, daily for 2 weeks) in a crossover intervention experiment was performed. In the present study, we did pathway-based metagenomic analyses on samples from a subset of individuals (n= 12) from that study to obtain additional detailed insights into the functional structure at high resolution during RS2 intervention. A mechanistic framework based on obtained results is proposed where primary degradation was governed byFirmicutes, withRuminococcus bromiias a major taxon involved, providing fermentation substrates and increased acetate concentrations for the growth of various major butyrate producers exhibiting the enzyme butyryl-coenzyme A (CoA):acetate CoA-transferase. H2-scavenging sulfite reducers and acetogens concurrently increased. Individual responses of gut microbiota were noted, where seven of the 12 participants displayed all features of the outlined pattern, whereas four individuals showed mixed behavior and one subject was unresponsive. Intervention order did not affect the outcome, emphasizing a constant substrate supply for maintaining specific functional communities.IMPORTANCEManipulation of gut microbiota is increasingly recognized as a promising approach to reduce various noncommunicable diseases, such as obesity and type 2 diabetes. Specific dietary supplements, including resistant starches (RS), are often a focus, yet comprehensive insights into functional responses of microbiota are largely lacking. Furthermore, unresponsiveness in certain individuals is poorly understood. Our data indicate that distinct parts of microbiota work jointly to degrade RS and successively form health-promoting fermentation end products. It highlights the need to consider both primary degraders and specific more-downstream-acting bacterial groups in order to achieve desired intervention outcomes. The gained insights will assist the design of personalized treatment strategies based on an individual's microbiota.

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Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00221.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. E52-E61

Author(s):

Na Rae Shin ◽

Namyi Gu ◽

Han Seok Choi ◽

Hojun Kim

Keyword(s):

Type 2 Diabetes ◽

Placebo Group ◽

Glucose Tolerance ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Metabolic Diseases ◽

Scutellaria Baicalensis ◽

Rrna Gene ◽

Microbiota Composition

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

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16S rRNA Sequencing and Metagenomics Study of Gut Microbiota: Implications of BDB on Type 2 Diabetes Mellitus

Marine Drugs ◽

10.3390/md18090469 ◽

2020 ◽

Vol 18 (9) ◽

pp. 469

Author(s):

Liang Zhang ◽

Jiao Luo ◽

Xiangqian Li ◽

Shuju Guo ◽

Dayong Shi

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

16S Rrna ◽

Gut Microbiota ◽

Critical Role ◽

Fasting Blood Glucose ◽

Rrna Gene ◽

Diabetic Mice

Gut microbiota has a critical role in metabolic diseases, including type 2 diabetes mellitus (T2DM). 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a natural bromophenol isolated from marine red alga Rhodomela confervoides. Our latest research showed that BDB could alleviate T2DM in diabetic BKS db mice. To find out whether BDB modulates the composition of the gut microbiota during T2DM treatment, 24 BKS db diabetic mice were randomly grouped to receive BDB (n = 6), metformin (n = 6), or the vehicle (n = 6) for 7 weeks in a blinded manner. Non-diabetic BKS mice (n = 6) were used as normal control. Diabetic mice treated with BDB or metformin demonstrated significant reductions in fasting blood glucose (FBG) levels compared with the vehicle-treated mice in the 7th week. Pyrosequencing of the V3–V4 regions of the 16S rRNA gene revealed the changes of gut microbiota in response to BDB treatment. The result demonstrated short-chain acid (SCFA) producing bacteria Lachnospiraceae and Bacteroides were found to be significantly more abundant in the BDB and metformin treated group than the vehicle-treatment diabetic group. Remarkably, at the genus levels, Akkermansia elevated significantly in the BDB-treatment group. Metagenomic results indicated that BDB may alleviate the metabolic disorder of diabetic mice by promoting propanoate metabolism and inhibiting starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism. In conclusion, our study suggests that the anti-diabetic effect of BDB is closely related to the modulating structure of gut microbiota and the improvement of functional metabolism genes of intestinal microorganisms.

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Gut dysbiosis, inflammation and type 2 diabetes in mice using synthetic gut microbiota from diabetic humans

Brazilian Journal of Biology ◽

10.1590/1519-6984.242818 ◽

2023 ◽

Vol 83 ◽

Author(s):

I. Liaqat ◽

N. M. Ali ◽

N. Arshad ◽

S. Sajjad ◽

F. Rashid ◽

...

Keyword(s):

Type 2 Diabetes ◽

16S Rrna ◽

Lactobacillus Acidophilus ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Gut Dysbiosis ◽

Rrna Gene Sequencing ◽

Modified Diet

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .

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The gut microbiome and type 2 diabetes status in the Multiethnic Cohort

PLoS ONE ◽

10.1371/journal.pone.0250855 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0250855

Author(s):

Gertraud Maskarinec ◽

Phyllis Raquinio ◽

Bruce S. Kristal ◽

Veronica W. Setiawan ◽

Lynne R. Wilkens ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiome ◽

Diversity Index ◽

16S Rrna Gene Sequencing ◽

Sensu Stricto ◽

Rrna Gene ◽

Cross Sectional ◽

Multiethnic Cohort ◽

Diabetes Status

Background The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP). Methods In 2013–16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1,702 participants (59.9–77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D. Conclusions T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.

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