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17 pages, 4228 KiB

Open AccessArticle

Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment

by Harinder Singh, Satoshi Miyamoto, Manjula Darshi, Manolito G. Torralba, Keehwan Kwon, Kumar Sharma and Rembert Pieper

Microorganisms 2020, 8(9), 1347; https://doi.org/10.3390/microorganisms8091347 - 3 Sep 2020

Cited by 26 | Viewed by 4204

Abstract

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of [...] Read more.

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice. Treatment with long-acting pirfenidone (PFD) increased gut microbial diversity in diabetic db/db mice. Firmicutes, the most abundant phylum in db/m mice, decreased significantly in abundance in db/db mice but showed increased abundance with long-acting PFD treatment. Several bacterial taxa, including Lactobacillus and some Bacteroides, were less abundant in db/db mice and more abundant in long-acting-PFD-treated db/db mice. Long-acting PFD treatment reduced the abundance of Akkermansia muciniphila (5%) as compared to db/db mice (~15%). We conclude that gut microbial dysbiosis observed in db/db mice was partially reversed by long-acting PFD treatment and hypothesize that PFD has beneficial effects, in part, via its influence on the gut microbial metabolite profile. In quantitatively assessing urine metabolites, we observed a high abundance of diabetic ketoacidosis biomarkers, including 3-hydroxybutyric acid and acetoacetic acid in db/db mice, which were less abundant in the long-acting-PFD-treated db/db mice. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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17 pages, 5437 KiB

Open AccessArticle

Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota

by Yinzhao Zhong, Bo Song, Changbing Zheng, Shiyu Zhang, Zhaoming Yan, Zhiyi Tang, Xiangfeng Kong, Yehui Duan and Fengna Li

Microorganisms 2020, 8(6), 860; https://doi.org/10.3390/microorganisms8060860 - 7 Jun 2020

Cited by 38 | Viewed by 3290

Abstract

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for [...] Read more.

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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13 pages, 2229 KiB

Open AccessCommunication

Characterization of the Duodenal Mucosal Microbiome in Obese Adult Subjects by 16S rRNA Sequencing

by Carmela Nardelli, Ilaria Granata, Valeria D'Argenio, Salvatore Tramontano, Debora Compare, Mario Rosario Guarracino, Gerardo Nardone, Vincenzo Pilone and Lucia Sacchetti

Microorganisms 2020, 8(4), 485; https://doi.org/10.3390/microorganisms8040485 - 29 Mar 2020

Cited by 43 | Viewed by 4075

Abstract

The gut microbiota may have an impact on obesity. To date, the majority of studies in obese patients reported microbiota composition in stool samples. The aim of this study was to investigate the duodenal mucosa dysbiosis in adult obese individuals from Campania, a [...] Read more.

The gut microbiota may have an impact on obesity. To date, the majority of studies in obese patients reported microbiota composition in stool samples. The aim of this study was to investigate the duodenal mucosa dysbiosis in adult obese individuals from Campania, a region in Italy with a very high percentage of obese people, to highlight microbial taxa likely associated with obesity. Duodenum biopsies were taken during upper gastrointestinal endoscopy in 19 obese (OB) and 16 lean control subjects (CO) and microbiome studied by 16S rRNA gene sequencing. Duodenal microbiome in our groups consisted of six phyla: Proteobacteria, Firmicutes, Actinobacteria, Fusobacteria, Bacteroidetes and Acidobacteria. Proteobacteria (51.1% vs. 40.1%) and Firmicutes (33.6% vs. 44.9%) were significantly (p < 0.05) more and less abundant in OB compared with CO, respectively. Oribacterium asaccharolyticum, Atopobium parvulum and Fusobacterium nucleatum were reduced (p < 0.01) and Pseudomonadales were increased (p < 0.05) in OB compared with CO. Receiver operating characteristic curve analysis showed Atopobium and Oribacterium genera able to discriminate with accuracy (power = 75% and 78%, respectively) OB from CO. In conclusion, increased Proteobacteria and decreased Firmicutes (Lachnospiraceae) characterized the duodenal microbiome of obese subjects. These data direct to further studies to evaluate the functional role of the dysbiotic-obese-associated signature. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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17 pages, 4378 KiB

Open AccessArticle

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

by Weida Wu, Li Zhang, Bing Xia, Shanlong Tang, Lei Liu, Jingjing Xie and Hongfu Zhang

Microorganisms 2020, 8(1), 111; https://doi.org/10.3390/microorganisms8010111 - 13 Jan 2020

Cited by 38 | Viewed by 4935

Abstract

Inulin (INU) is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. However, whether and how gut microbiota in its regulation contributes to host metabolism has yet to be investigated. We conduct this study to examine the possible associations between the [...] Read more.

Inulin (INU) is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. However, whether and how gut microbiota in its regulation contributes to host metabolism has yet to be investigated. We conduct this study to examine the possible associations between the gut microbiota and circulating gut microbiota–host co-metabolites induced by inulin interventions. Plasma and intestinal site samples were collected from the pigs that have consumed inulin diet for 60 days. High-throughput sequencing was adopted for microbial composition, and the GC-TOF-MS-based metabolomics were used to characterize featured plasma metabolites upon inulin intervention. Integrated multi-omics analyses were carried out to establish microbiota–host interaction. Inulin consumption decreased the total cholesterol (p = 0.04) and glucose (p = 0.03) level in serum. Greater β-diversity was observed in the cecum and colon of inulin-fed versus that of control-fed pigs (p < 0.05). No differences were observed in the ileum. In the cecum, 18 genera were altered by inulin, followed by 17 in the colon and 6 in the ileum. Inulin increased propionate, and isobutyrate concentrations but decreased the ratio of acetate to propionate in the cecum, and increased total short fatty acids, valerate, and isobutyrate concentrations in the colon. Metabolomic analysis reveals that indole-3-propionic acid (IPA) was significantly higher, and the branched-chain amino acids (BCAA), L-valine, L-isoleucine, and L-leucine are significantly lower in the inulin groups. Mantel test and integrative analysis revealed associations between plasma metabolites (e.g., IPA, BCAA, L-tryptophan) and inulin-responsive cecal microbial genera. These results indicate that the inulin has regional effects on the intestine microbiome in pigs, with the most pronounced effects occurring in the cecum. Moreover, cecum microbiota plays a pivotal role in the modulation of circulating host metabolites upon inulin intervention Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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16 pages, 3013 KiB

Open AccessArticle

Characterization of the Gut Microbiota of Individuals at Different T2D Stages Reveals a Complex Relationship with the Host

by Alejandra Chávez-Carbajal, María Luisa Pizano-Zárate, Fernando Hernández-Quiroz, Guillermo Federico Ortiz-Luna, Rosa María Morales-Hernández, Amapola De Sales-Millán, María Hernández-Trejo, Angelina García-Vite, Luis Beltrán-Lagunes, Carlos Hoyo-Vadillo and Jaime García-Mena

Microorganisms 2020, 8(1), 94; https://doi.org/10.3390/microorganisms8010094 - 10 Jan 2020

Cited by 64 | Viewed by 5967

Abstract

In this work, we studied 217 Mexican subjects divided into six groups with different stages of glucose intolerance: 76 Controls (CO), 54 prediabetes (PRE), 14 T2D no medication (T2D−No−M), 14 T2D with Metformin (T2D−M), 22 T2D with polypharmacy (T2D−P), and 37 T2D with [...] Read more.

In this work, we studied 217 Mexican subjects divided into six groups with different stages of glucose intolerance: 76 Controls (CO), 54 prediabetes (PRE), 14 T2D no medication (T2D−No−M), 14 T2D with Metformin (T2D−M), 22 T2D with polypharmacy (T2D−P), and 37 T2D with polypharmacy and insulin (T2D−P+I). We aimed to determine differences in the gut microbiota diversity for each condition. At the phylum level, we found that Firmicutes and Bacteroidetes outline major changes in the gut microbiota. The gut bacterial richness and diversity of individuals in the T2D−No−M group were lesser than other groups. Interestingly, we found a significant difference in the beta diversity of the gut microbiota among all groups. Higher abundance was found for Comamonadaceae in PRE, and Sutterella spp. in T2D−No−M. In addition, we found associations of specific microbial taxa with clinical parameters. Finally, we report predicted metabolic pathways of gut microbiota linked to T2D−M and PRE conditions. Collectively, these results indicate that each group has specific predicted metabolic characteristics and gut bacteria populations for each phenotype. The results of this study could be used to define strategies to modulate gut microbiota through noninvasive treatments, such as dietary intervention, probiotics or prebiotics, and to improve glucose tolerance of individuals with prediabetes or T2D. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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14 pages, 6579 KiB

Open AccessArticle

Profiling the Oral Microbiome and Plasma Biochemistry of Obese Hyperglycemic Subjects in Qatar

by Muhammad U. Sohail, Mohamed A. Elrayess, Asma A. Al Thani, Maha Al-Asmakh and Hadi M. Yassine

Microorganisms 2019, 7(12), 645; https://doi.org/10.3390/microorganisms7120645 - 3 Dec 2019

Cited by 17 | Viewed by 4990

Abstract

The present study is designed to compare demographic characteristics, plasma biochemistry, and the oral microbiome in obese (N = 37) and lean control (N = 36) subjects enrolled at Qatar Biobank, Qatar. Plasma hormones, enzymes, and lipid profiles were analyzed at [...] Read more.

The present study is designed to compare demographic characteristics, plasma biochemistry, and the oral microbiome in obese (N = 37) and lean control (N = 36) subjects enrolled at Qatar Biobank, Qatar. Plasma hormones, enzymes, and lipid profiles were analyzed at Hamad Medical Cooperation Diagnostic Laboratory. Saliva microbiome characterization was carried out by 16S rRNA amplicon sequencing using Illumina MiSeq platform. Obese subjects had higher testosterone and sex hormone-binding globulin (SHBG) concentrations compared to the control group. A negative association between BMI and testosterone (p < 0.001, r = −0.64) and SHBG (p < 0.001, r = −0.34) was observed. Irrespective of the study groups, the oral microbiome was predominantly occupied by Streptococcus, Prevotella, and Veillonella species. A generalized linear model revealed that the Firmicutes/Bacteroidetes ratio (2.25 ± 1.83 vs. 1.76 ± 0.58; corrected p-value = 0.04) was higher, and phylum Fusobacteria concentration (4.5 ± 3.0 vs. 6.2 ± 4.3; corrected p-value = 0.05) was low in the obese group compared with the control group. However, no differences in microbiome diversity were observed between the two groups as evaluated by alpha (Kruskal–Wallis p ≥ 0.78) and beta (PERMANOVA p = 0.37) diversity indexes. Certain bacterial phyla (Acidobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Firmicutes/Bacteroidetes) were positively associated (p = 0.05, r ≤ +0.5) with estradiol, fast food consumption, creatinine, breastfed during infancy, triglycerides, and thyroid-stimulating hormone concentrations. In conclusion, no differences in oral microbiome diversity were observed between the studied groups. However, the Firmicutes/Bacteroidetes ratio, a recognized obesogenic microbiome trait, was higher in the obese subjects. Further studies are warranted to confirm these findings in a larger cohort. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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17 pages, 547 KiB

Open AccessArticle

Predictors of Obesity among Gut Microbiota Biomarkers in African American Men with and without Diabetes

by Elena Barengolts, Stefan J. Green, George E. Chlipala, Brian T. Layden, Yuval Eisenberg, Medha Priyadarshini and Lara R. Dugas

Microorganisms 2019, 7(9), 320; https://doi.org/10.3390/microorganisms7090320 - 5 Sep 2019

Cited by 22 | Viewed by 4655

Abstract

Gut microbiota and their biomarkers may be associated with obesity. This study evaluated associations of body mass index (BMI) with circulating microbiota biomarkers in African American men (AAM) (n = 75). The main outcomes included fecal microbial community structure (16S rRNA), gut [...] Read more.

Gut microbiota and their biomarkers may be associated with obesity. This study evaluated associations of body mass index (BMI) with circulating microbiota biomarkers in African American men (AAM) (n = 75). The main outcomes included fecal microbial community structure (16S rRNA), gut permeability biomarkers (ELISA), and short-chain fatty acids (SCFAs, metabolome analysis). These outcomes were compared between obese and non-obese men, after adjusting for age. The results showed that lipopolysaccharide-binding protein (LBP), the ratio of LBP to CD14 (LBP/CD14), and SCFAs (propionic, butyric, isovaleric) were higher in obese (n = 41, age 58 years, BMI 36 kg/m²) versus non-obese (n = 34, age 55 years, BMI 26 kg/m²) men. BMI correlated positively with LBP, LBP/CD14 (p < 0.05 for both) and SCFAs (propionic, butyric, isovaleric, p < 0.01 for all). In the regression analysis, LBP, LBP/CD14, propionic and butyric acids were independent determinants of BMI. The study showed for the first time that selected microbiota biomarkers (LBP, LBP/CD14, propionic and butyric acids) together with several other relevant risks explained 39%–47% of BMI variability, emphasizing that factors other than microbiota-related biomarkers could be important. Further research is needed to provide clinical and mechanistic insight into microbiota biomarkers and their utility for diagnostic and therapeutic purposes. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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Review

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24 pages, 3177 KiB

Open AccessReview

Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

by Kaliyan Barathikannan, Ramachandran Chelliah, Momna Rubab, Eric Banan-Mwine Daliri, Fazle Elahi, Dong-Hwan Kim, Paul Agastian, Seong-Yoon Oh and Deog Hwan Oh

Microorganisms 2019, 7(10), 456; https://doi.org/10.3390/microorganisms7100456 - 16 Oct 2019

Cited by 59 | Viewed by 11634

Abstract

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to [...] Read more.

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed. Full article

(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)

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