This study sought to explore the correlation between metformin and Akkermansia muciniphila (Akk), aiming to clarify the molecular mechanism of their synergistic effects. Akk standard strain JCM30893 was cultured in an optimized medium supplemented with 4 mmol/L metformin. Under this condition, we observed significant growth promotion of Akk, as evidenced by enhanced consumption of sugars and proteins and alterations in pH. Notably, metformin treatment significantly increased the production of arginine by Akk, along with an elevated production of short-chain fatty acids (butyrate, isovalerate, isobutyrate, and acetate). Untargeted metabolomics further confirmed that metformin up-regulated therapeutic metabolites, including arginine, L-carnitine, and nicotinamide, which are associated with antidiabetic, anti-inflammatory, cardiovascular protective, and anticancer properties. Additionally, metabolic pathways linked to protein digestion, nucleotide metabolism, and arginine biosynthesis were found to be enhanced in the metformin-treated group. These findings provide a molecular framework for elucidating the synergistic therapeutic effects of metformin and Akk in the treatment of diabetes and obesity, offering insights into potential combination therapies.
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Open Access
Issue
Open Access
Basic Research
Issue
Fusobacterium nucleatum (Fn), a common conditioned oral pathogen, has been found to be able to protect colon, breast and lung cancer cells against antibiotics and promote their proliferation and metastasis. The purpose of this study was to explore the inhibitory effect and mechanism of L-3-phenyllactic acid on Fn to provide directions for cancer prevention through the consumption of natural biological acids. Based on its growth curve, the optimum growth period of Fn and the minimum inhibitory concentration (MIC) of phenyllactic acid against Fn were determined, and the changes in the morphology, integrity and damage degree of the Fn cell membrane under the action of phenyllactic acid were investigated for the purpose of evaluating the ability of phenyllactic acid to inhibit Fn. The results showed that the optimum growth period of Fn was 27 h, and that the MIC of phenyllactic acid on Fn was 0.50 mg/mL. Treatment with phenyllactic acid at the MIC for 2 h increased the cell membrane permeability and changed significantly the cell morphology of Fn. Phenyllactic acid could disrupt the biofilm formed by Fn and reduce Fn adhesion. This study confirmed that phenyllactic acid had the ability to destroy the cell membrane structure of Fn and inhibit its biofilm-forming ability, thereby leading to the leakage of cellular contents and a reduction in the intracellular protein content.
Open Access
Issue
Undigested components from a large intake of red meat can be fermented by the intestinal flora to form harmful metabolites, thereby destroying intestinal homeostasis and increasing the risk of colon cancer and cardiovascular diseases. To explore the effect of dietary addition of inulin or soybean dietary fiber (SDF) on the intestinal flora and metabolites in mice fed a beef-containing diet, male C57BL/6Cnc mice were randomly divided into a blank control group, a beef group, a beef plus inulin group, and a beef plus SDF group. The intestinal flora structure of mice was detected by high-throughput 16S rRNA gene sequencing. The concentrations of short-chain fatty acids (SCFAs) in the colon contents were detected by gas chromatography-mass spectrometry (GC-MS), and the content of trimethylamine oxide (TMAO) in the kidney was determined. The results showed that in the beef group, the diversity of intestinal flora decreased significantly (P < 0.05), the abundance of Firmicutes, Lactobacillus and Clostridium_sensu_stricto_1 increased, and the abundance of beneficial bacteria such as Bifidobacterium and Faecalibaculum decreased; the contents of SCFAs in the colon contents decreased, and the content of TMAO increased significantly (P < 0.05). Dietary addition of inulin or SDF significantly improved the diversity of intestinal flora in mice (P < 0.05); inulin increased the abundance of Bifidobacterium and Ruminococcaceae_UCG_014, while SDF increased the abundance of Akkermansia and Faecalibaculum. Both dietary fibers increased the content of SCFAs in the colon contents and decreased the concentration of TMAO in the kidney (P < 0.05). In conclusion, beef intake does have a negative impact on the intestinal flora and metabolites in mice, and this effect can be blocked by addition of dietary fiber to the diet, thereby reducing the risk of various related diseases. These results can provide a theoretical and scientific basis for the development of a reasonable diet and personalized precise nutrition in the future.
Open Access
Review
Issue
Depression is one of the most common mental disorders in modern society. The disease not only seriously harms people’s quality of life, but also brings a huge burden to families and society because of the high suicide rate and disability rate caused by it. Recent studies have shown that the intestinal flora plays an important role the occurrence and progression of depression and dysfunctional gut-brain communication may be an essential pathological mechanism of depression. The“microbiota-gut-brain” (MGB) axis allows the intestinal flora to participate in the two-way information exchange between the intestine and the brain. Most previous studies mainly focus on exploring the individual characteristics of the intestinal flora in patients with depression and the relationship between the intestinal flora and the occurrence of depression, revealing that maintaining a healthy intestinal flora may be a new idea for the prevention and treatment of depression in the future. This article summarizes recent progress in this research field. We hope that this review can provide insights into the action mechanism of anti-depressive agents from the perspective of the MGB axis, and also provide a reference for the application of probiotics in new depression treatments.
Open Access
Review
Issue
The global prevalence of obesity has nearly tripled in the past 40 years and continues to rise at an alarming rate. High fat and high carbohydrate diets can cause gut microbiota disturbance and impairment of intestinal barrier function in obese individuals. Dysbiosis of the gut microbiota and its metabolites crossing the intestinal barrier lead to insulin resistance, imbalance in energy metabolism, reduced fat browning capacity and increased levels of inflammatory factors, which in turn induce chronic diseases such as diabetes, hypertension and cardiovascular diseases. In this paper, the molecular mechanism of obesity mediated by the gut microbiota is systematically elucidated. Based on this, we propose that the intestinal microecology can be regulated by supplementing probiotics and prebiotics or by changing lifestyle and dietary pattern, which in turn will help to prevent and control obesity.
Open Access
Review
Issue
Diabetes is a metabolic disease characterized by insulin secretion disorder. When serious, it can cause various complications (cardiovascular and cerebrovascular diseases, cataract and other eye diseases, kidney disease and cancer), bringing a huge economic burden to the society and families and torturing patients. The risk of diabetes is not only related to genes, living pressure and working environment, but also directly related to patients’ lifestyles and dietary habits. An unhealthy diet (high in fat and sugar) can induce the intestinal flora to produce adverse metabolites, which can in turn promote the occurrence and development of diabetes. Intestinal flora imbalance is widespread in the pathogenesis of various types of diabetes. As an important factor influencing the intestinal flora, diet is not only essential to maintain body functions, but also can contribute to intestinal immunity. Regulation of the intestinal environment through diet is expected to be an effective preventive means and auxiliary therapy for diabetes. By synthesizing the existing literature, this article discusses the features of the intestinal flora and the mechanism of the effect of diet-mediated regulation of the intestinal flora on diabetes based on systematic medical theory, and reviews the role scientific diet plays in regulating intestinal homeostasis and immunity and consequently reducing the incidence and complications of diabetes. We hope that this review will provide a basis for early diagnosis and prevention and adjuvant treatment of diabetes.
Open Access
Issue
In this study, Akkermansia muciniphila (Akk) was cultured to a concentration of more than 109 CFU/mL in optimized liquid thioglycolate medium. Besides, the differential metabolites in the fermentation supernatants from the original and optimized medium were analyzed by non-targeted metabolomics, and the physiological functions of the characteristic products were evaluated. The results showed that when cultured in the optimized medium, Akk produced higher amounts of various functional metabolites such as propionic acid, bardoxifene, docetaxel and vinblastine by affecting protein digestion and absorption, aminoacyl tRNA biosynthesis, bile secretion, ATP-binding cassette (ABC) transporter, and the metabolic pathways of amino acid biosynthesis. These metabolites could be directly related to anti-cancer, anti-inflammatory, anti-obese and other functions. This study provides solid evidence that Akk can function as a probiotic agent and postbiotic to regulate many diseases, and lays a theoretical foundation for future industrial production.
Open Access
Research Article
Issue
Although monosodium glutamate (MSG) is a widely used food additive, its safety and systemic side effects have not been fully clarified. The intestinal flora is closely associated with human health; however, it remains unclear whether MSG consumption can affect health by acting on the intestinal flora. In this study, serum biomarkers, intestinal structure, intestinal immunity, and intestinal flora were examined to investigate the effects of different doses of sodium glutamate on the body, intestinal function, and intestinal flora of mice. The results showed that 30mg/kg MSG had no significant effect on serum C-reactive protein, trimethylamine N-oxide, angiotensin II, intestinal interleukin (IL)-1β, IL-6, tumor necrosis factor-α, secretory IgA and fecal albumin in mice, but also promoted intestinal development and regulated the intestinal flora. Moreover, 1500 mg/kg MSG increased the risk of cardiovascular disease and damaged the intestinal structure and flora. In this study, MSG was also found to be healthier than salt at the equivalent sodium concentration. Collectively, these findings suggested that low doses of MSG were safe for mice and may have some health benefits as a probiotic by promoting intestinal development and regulating the intestinal flora.
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