Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family.
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ABSTRACT:
SUBMITTER: Du J
PROVIDER: S-EPMC7889173 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A Western diet comprising high fat, high carbohydrate, and low fiber content has been suggested to contribute to an increased prevalence of colitis. To clarify the effect of dietary cellulose (an insoluble fiber) on gut homeostasis, for 3 months mice were fed a high-cellulose diet (HCD) or a low-cellulose diet (LCD) based on the AIN-93G formulation. Histologic evaluation showed crypt atrophy and goblet cell depletion in the colons of LCD-fed mice. RNA-sequencing analysis showed a higher expression of genes associated with immune system processes, especially those of chemokines and their receptors, in the colon tissues of LCD-fed mice than in those of HCD-fed mice. The HCD was protective against dextran sodium sulfate-induced colitis in mice, while LCD exacerbated gut inflammation; however, the depletion of gut microbiota by antibiotic treatment diminished both beneficial and non-beneficial effects of the HCD and LCD on colitis, respectively. A comparative analysis of the cecal contents of mice fed the HCD or the LCD showed that the LCD did not influence the diversity of gut microbiota, but it resulted in a higher and lower abundance of Oscillibacter and Akkermansia organisms, respectively. Additionally, linoleic acid, nicotinate, and nicotinamide pathways were most affected by cellulose intake, while the levels of short-chain fatty acids were comparable in HCD- and LCD-fed mice. Finally, oral administration of Akkermansia muciniphila to LCD-fed mice elevated crypt length, increased goblet cells, and ameliorated colitis. These results suggest that dietary cellulose plays a beneficial role in maintaining gut homeostasis through the alteration of gut microbiota and metabolites.
| S-EPMC7524403 | biostudies-literature
Project description:Early life is a critical window for preventing the intergenerational transmission of metabolic diseases. Betaine has been proven to play a role in improving glucose and lipid metabolism disorders in animal models. However, whether maternal betaine supplementation plays a role in regulating gut microbiota in both dams and offspring remains unclear. In this study, C57BL/6 female mice were fed with control diet (Ctr), high-fat diet (HF), and high-fat with betaine supplementation (0.3% betaine in the diet, HFB) from 3 weeks prior to mating and lasted throughout pregnancy and lactation. After weaning, the offspring got free access to normal chow diet until 20 weeks of age. We found that maternal dietary betaine supplementation significantly improved glucose and insulin resistance, as well as reduced free fatty acid (FFA) concentration in dams and offspring from young to adult. When compared to the HF group, Intestinimonas and Acetatifactor were reduced by betaine supplementation in dams; Desulfovibrio was reduced in 4-week-old offspring of the HFB group; and Lachnoclostridium was enriched in 20-week-old offspring of the HFB group. Moreover, the persistent elevated genus Romboutsia in both dams and offspring in the HFB group was reported for the first time. Overall, maternal betaine could dramatically alleviate the detrimental effects of maternal overnutrition on metabolism in both dams and offspring. The persistent alterations in gut microbiota might play critical roles in uncovering the intergenerational metabolic benefits of maternal betaine, which highlights evidence for combating generational metabolic diseases.
| S-EPMC9037091 | biostudies-literature
Project description:Evidence suggests that altered gut microbiota composition may be involved in the development of obesity. Studies using mice made obese with refined high-fat diets have supported this; however, these have commonly used chow as a control diet, introducing confounding factors from differences in dietary composition that have a key role in shaping microbiota composition. We compared the effects of feeding a refined high-fat diet with those of feeding either a refined low-fat diet or a chow diet on gut microbiota composition and host physiology. Feeding both refined low- or high-fat diets resulted in large alterations in the gut microbiota composition, intestinal fermentation, and gut morphology, compared to a chow diet. However, body weight, body fat, and glucose intolerance only increased in mice fed the refined high-fat diet. The choice of control diet can dissociate broad changes in microbiota composition from obesity, raising questions about the previously proposed relationship between gut microbiota and obesity.
| S-EPMC5695904 | biostudies-other
Project description:Dietary fiber has been shown to prevent high-fat diet induced obesity through modulating the gut microbiota; however, quality difference in fiber type is largely unknown. We performed a 6 week study on C57BL/6J mice fed a macronutrient matched high-fat diet with different fiber types including cellulose (HFC), bamboo shoot fiber (HFBS) and several other commonly consumed fibers. Our results showed that the HFBS group exhibited the lowest weight gain among all diet groups and had improved lipid profiles and glycemic control compared with the HFC group. As revealed by 16S rRNA gene sequencing, loss of diversity in the gut microbiota induced by the HFC diet was largely prevented by the HFBS diet. Moreover, compared with the HFC diet, the HFBS diet resulted in markedly increased relative abundance of Bacteroidetes and strong inhibition of Verrucomicrobia, two divisions strongly correlated with body weight. In conclusion, the present study provides evidence of a quality difference among different types of dietary fibers and shows that bamboo shoot fiber is the most effective in suppressing high-fat diet induced obesity. Our findings indicate that bamboo shoot fiber is a potential prebiotic fiber which modulates the gut microbiota and improves host metabolism.
| S-EPMC5013436 | biostudies-literature
Project description:BACKGROUND:Accumulating evidence is supporting the protective effect of whole grains against several chronic diseases. Simultaneously, our knowledge is increasing on the impact of gut microbiota on our health and on how diet can modify the composition of our bacterial cohabitants. Herein, we studied C57BL/6?J mice fed with diets enriched with rye bran and wheat aleurone, conventional and germ-free C57BL/6NTac mice on a basal diet, and the colonic fermentation of rye bran in an in vitro model of the human gastrointestinal system. We performed 16S rRNA gene sequencing and metabolomics on the study samples to determine the effect of bran-enriched diets on the gut microbial composition and the potential contribution of microbiota to the metabolism of a novel group of betainized compounds. RESULTS:The bran-enriched study diets elevated the levels of betainized compounds in the colon contents of C57BL/6?J mice. The composition of microbiota changed, and the bran-enriched diets induced an increase in the relative abundance of several bacterial taxa, including Akkermansia, Bifidobacterium, Coriobacteriaceae, Lactobacillus, Parasutterella, and Ruminococcus, many of which are associated with improved health status or the metabolism of plant-based molecules. The levels of betainized compounds in the gut tissues of germ-free mice were significantly lower compared to conventional mice. In the in vitro model of the human gut, the production of betainized compounds was observed throughout the incubation, while the levels of glycine betaine decreased. In cereal samples, only low levels or trace amounts of other betaines than glycine betaine were observed. CONCLUSIONS:Our findings provide evidence that the bacterial taxa increased in relative abundance by the bran-based diet are also involved in the metabolism of glycine betaine into other betainized compounds, adding another potential compound group acting as a mediator of the synergistic metabolic effect of diet and colonic microbiota.
| S-EPMC6621954 | biostudies-literature
Project description:ObjectiveGut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice.MethodsGF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing.ResultsGF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes) as a characteristic feature of normal SPF mice fed lard.ConclusionsIn conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.
| S-EPMC5123202 | biostudies-literature
Project description:Gut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.
| S-EPMC8080667 | biostudies-literature
Project description:BackgroundInhibitors of ornithine decarboxylase (ODC) are effective at preventing colorectal cancer (CRC). However, their high toxicity limits their clinical application. This study was aimed to explore the potential of microRNAs (miRNAs) as an inhibitor of ODC.MethodsmiRNA array was used to identify dysregulated miRNAs in CRC tumors of mice and patients. Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) were used to induce CRC in mice. miRNA function in carcinogenesis was determined by soft-agar colony formation, flow cytometry, and wound healing of CRC cells. Mini-circle was used to deliver miRNA into colons.ResultsMiRNA profiling identified miR-378a-3p (miR-378a) as the most reduced miRNA in CRC tumors of patients and mice treated with AOM/DSS. Pathway array analysis revealed that miR-378a impaired c-MYC and ODC1 pathways. Further studies identified FOXQ1 (forkhead box Q1) and ODC1 as two direct targets of miR-378a. FOXQ1 activated transcription of c-MYC, a transcription activator of ODC1. In addition to directly targeting ODC1, miR-378a also inhibited expression of ODC1 via the FOXQ1-cMYC axis, thereby inhibiting polyamine synthesis in human CRC cells. Phenotypically, by reducing polyamine synthesis, miR-378a induced apoptosis and inhibited proliferation and migration of CRC cells, while disrupting the association of miR-378a with FOXQ1 and ODC1 offset the effects of miR-378a, suggesting that FOXQ1 and ODC1 were required for miR-378a to inhibit CRC cell growth. MiR-378a treatment robustly prevented growth of HCC by inhibiting polyamine synthesis in AOM/DSS mice.ConclusionMiR-378a prevents CRC by inhibiting polyamine synthesis, suggesting its use as a novel ODC inhibitor against CRC.
| S-EPMC9717536 | biostudies-literature
Project description:Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.
| S-EPMC6728375 | biostudies-literature
Project description:The dynamics and diversity of human gut microbiota that can remarkably influence the wellbeing and health of the host are constantly changing through the host's lifetime in response to various factors. The aim of the present study was to determine a set of parameters that could have a major impact on classifying subjects into a single cluster regarding gut bacteria composition. Therefore, a set of demographical, environmental, and clinical data of healthy adults aged 25-50 years (117 female and 83 men) was collected. Fecal microbiota composition was characterized using Illumina MiSeq 16S rRNA gene amplicon sequencing. Hierarchical clustering was performed to analyze the microbiota data set, and a supervised machine learning model (SVM; Support Vector Machines) was applied for classification. Seventy variables from collected data were included in machine learning analysis. The agglomerative clustering algorithm suggested the presence of four distinct community types of most abundant bacterial phyla. Each cluster harbored a statistically significant different proportion of bacterial phyla. Regarding prediction, the most important features classifying subjects into clusters were measures of obesity (waist to hip ratio, BMI, and visceral fat index), total body water, blood pressure, energy intake, total fat, olive oil intake, total fiber intake, and water intake. In conclusion, the SVM model was shown as a valuable tool to classify healthy individuals based on their gut microbiota composition.
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