Improvement effect of Wumei on antibiotic induced intestinal microbiota imbalance in mice
The origin of medicine and food is rooted in traditional Chinese medicine culture, which refers to the fact that both medicine and food come from nature. Under the guidance of traditional Chinese medicine theory, they are based on primary and secondary metabolites as the material basis, and play a role in regulating, rehabilitating, and promoting health. The homology of medicine and food reflects the unique advantages of traditional Chinese medicine, which plays a synergistic role in disease treatment and an important role in disease prevention and rehabilitation. On the basis of a thorough assessment of the safety of traditional medicinal and edible dual-use substances, China has formulated the “List of Items that are Both Food and Drug” (hereinafter referred to as the “List”), which includes 93 traditional Chinese medicines with traditional consumption habits and listed in the national Chinese herbal medicine standards (including the Pharmacopoeia of the People’s Republic of China and related Chinese herbal medicine standards). At present, there is an urgent need to use scientific theories to elucidate the efficacy and molecular mechanisms of drugs and food homologous substances. However, drugs and food homologous substances have a slow onset of action and are not suitable for the research approach of chemical drug targets. The gut microbiota provides us with a new perspective.

The gastrointestinal tract of the human body is rich in billions of microorganisms, and the genome encoded by these microorganisms is 50-100 times that of the human body’s own genes, known as the “second genome” of the human body. As a “special organ” of the human body, gut microbiota plays an important role in material and energy metabolism, neural and immune regulation, as well as resisting the invasion of pathogenic microorganisms. A large number of studies have shown that dysbacteriosis (changes in flora structure) is closely related to the occurrence and development of many diseases, such as cancer, infectious diseases, cardiovascular diseases, mental system diseases, etc. Medicinal and edible substances regulate the gut microbiota, playing a role in health preservation and disease prevention and treatment.

Ume is a dried near mature fruit of Prunus mume (Sieb.) Sieb. et Zucc. in the Rosaceae family, processed by smoking or baking methods. Ume has a long history of medicinal and edible use, first recorded in the “Shennong Bencao Jing” and classified as a medium grade; To include varieties in the “List” and widely integrate them into daily diet and health care, especially in Japan, there is a saying “please enjoy dried plums when drinking morning tea”. This substance is sour, astringent, and calm, and belongs to the liver, spleen, lungs, and large intestine meridians. It has the effects of tonifying the lungs, astringent intestines, generating fluids, and relieving roundworms. Research has shown that Ume is rich in organic acids, phenolic acids, flavonoids, terpenes, and steroids. Modern pharmacological studies have confirmed that Ume has various pharmacological effects such as antibacterial, cough suppressant, sedative hypnotic, anticonvulsant, antiviral, anti-tumor, and antioxidant properties. This study constructed a broad-spectrum antibiotic induced mouse gut microbiota dysbiosis model. High throughput sequencing technology was used to sequence the 16SrRNA gene of the gut microbiota of mice before and after intervention with Ume, and changes in body mass and inflammatory factors were detected to investigate the regulatory effect of Ume on antibiotic induced gut microbiota dysbiosis. From the perspective of gut microbiota, this study provides scientific basis for the medicinal and dietary application of Ume.

Ume medicine and food have a long history, integrating medical treatment, health care, and wellness. The book “Bencao Congxin” records that it can astringent the intestines and constrict the lungs, stop bleeding and phlegm, reduce swelling and detoxify, produce fluids and quench thirst, treat long-term cough and diarrhea, and is particularly good for blood dysentery. Clinical experts flexibly use the formula containing black plum to treat lung diseases such as asthma, allergic rhinitis, gastrointestinal diseases such as chronic gastritis, stubborn diarrhea, inflammatory bowel disease, intestinal malignant tumors, nervous system diseases such as headache, dizziness, insomnia, Parkinson’s disease, and metabolic diseases such as diabetes. As a traditional Chinese medicine with medicinal and edible properties, Ume has both nutritional and “supporting the body” effects, with high safety. Ume can be found in daily meals, tea drinks, and alcoholic beverages.

Both gut microbiota and traditional Chinese medicine emphasize balance, and once it is disrupted, it needs to be ‘corrected’ to restore balance. This study used broad-spectrum antibiotics commonly used in clinical practice, such as gentamicin sulfate and cefotaxime sodium, to induce a mouse model of intestinal microbiota dysbiosis by gavage (with a modeling dose approximately 10 times the maximum clinical dose for humans), to investigate the regulatory effect of wumei on microbiota dysbiosis, and explore its mechanism as a microecological regulator applied in clinical practice and health care. Through structural analysis of gut microbiota and detection of inflammatory factors, it was found that Ume can improve the disturbance of antibiotic induced microbiota and regulate inflammatory factors TNF – α, IL-1 β, and IL-6 to normal levels.

Healthy individuals typically experience hypoxia in their intestines, with anaerobic bacteria being the predominant microbiota and pathogenic facultative anaerobic bacteria being suppressed; In many disease states, the proliferation of facultative anaerobic bacteria indicates a dysbiosis of the gut microbiota. During metabolic and immune disorders, the host’s control over the intestinal ecosystem is impaired, and facultative anaerobic bacteria transform into dominant bacteria, marked by an increase in the phylum Proteobacteria (containing many opportunistic pathogens); Scholars have proposed using the amplification of Proteobacteria as a diagnostic feature for intestinal epithelial dysfunction and a potential biomarker for non communicable diseases such as obesity and asthma. High expression of Proteobacteria was observed in patients with type 2 diabetes, inflammatory bowel disease (IBD), mental illness and various respiratory diseases. The relative abundance of Proteobacteria in the model group of mice significantly increased, while the medium and low doses of Ume significantly decreased the relative abundance of Proteobacteria, which is consistent with the astringent and astringent effects of Ume on the intestines and lungs, as well as its ability to generate fluids and quench thirst.

Research has found that Lactobacillus rhamnosus and Lactobacillus crispus, which colonize the intestines of sterile mice, stimulate specific immune functions through granulocyte macrophage colony-2 (GM-CSF) to resist lung infections. Animal bifidobacteria mediate the anti influenza effect of sterile mice through several specific metabolic molecules, which may be used for preventing influenza and as a prognostic marker for influenza. The abundance of lactobacilli and bifidobacteria in the gut of mice has been shown to be correlated with the severity of malaria infection, and has potential value in regulating gut microbiota to reduce infection. DSS induced transplantation of Lactobacillus bacteria in IBD mice can reverse DSS induced colon shortening, reduce inflammation, and increase the number of colon stem cells. A study involving 17 obese individuals, 22 obese patients with type 2 diabetes, and 27 healthy individuals suggested that bifidobacteria may become biomarkers for the occurrence and development of type 2 diabetes and obesity. A cross-sectional study involving 1001 Japanese subjects aged 20 to 76 years showed a significant negative correlation between Blautia (Blautia genus) and visceral fat area (VFA). The Blautia genus in the feces of obese and obese children with insulin resistance is significantly reduced, while inflammatory factors are increased. In vitro monocyte cultures, specific species of Blautia genus exhibit anti-inflammatory effects. A randomized double-blind placebo-controlled trial involving 103 Malaysian adults showed that supplementing with Lactobacillus plantarum P8 can significantly alleviate stress and anxiety, reduce plasma inflammatory factors, and improve memory and cognitive abilities. In the study of colorectal cancer mouse models, it was found that Faecalibaculum rodentium can exert anti-tumor effects by producing short chain fatty acids.

This study showed that medium and low doses of Ume significantly upregulated Lactobacillus and Faecalibaculum at the genus level, while high and low doses of Ume significantly upregulated the relative abundance of Bifidobacterium and Blautia. Based on this, we speculate that Ume can mediate probiotics such as Lactobacillus, Bifidobacterium, Blautia, and Faecalibaculum, and exert preventive and therapeutic effects on pulmonary diseases, gastrointestinal inflammation and tumors, as well as metabolic and neurological diseases through the lung gut axis and gut brain axis. This is also consistent with the prediction results of PICRUSt.

This study investigated the improvement effect of Ume on chronic inflammation by detecting inflammatory factors. TNF – α initiates the inflammatory process and induces the regulation of secondary cytokine production, playing a central role not only in infection and inflammatory responses, but also in the growth, inhibition, and tissue damage of tumor cells; The serum TNF – α of model group mice increased significantly, which coincided with the prediction of PICRUSt function – the number of gene copies of cancer, infectious diseases, neurodegenerative disease and other subfunctions of model mice caused by antibiotics increased significantly. The TNF – α in plasma is influenced by visceral fat content, and the significant increase in body weight caused by antibiotics in mice may be one of the triggers for the significant upregulation of TNF – α in mice. IL-6 and IL-1 β are induced by TNF – α and mediate the acute phase of inflammatory response. Although IL-1 β and IL-6 in the model group mice decreased, they did not have statistical significance. Pathological sections also showed that antibiotics did not cause intestinal mucosal damage in mice in this experiment, indicating that the degree of inflammation caused by antibiotics in this experiment was relatively mild. By analyzing the gene copy number, it was found that low and medium doses of dark plum could reverse the significant increase of gene copy number predicted by four subfunctions of cancer, infectious diseases, neurodegenerative disease and energy metabolism caused by antibiotics. However, the improvement effect of low-dose Ume on inflammatory factors is not significant. Only medium dose Ume regulates TNF – α, IL-1 β, IL-6 to normal levels and has a weight loss effect. Ume has antibacterial effects, and the detection results of inflammatory factors also support that Ume inhibits the growth of pathogenic bacteria by interfering with their colonization in the intestine, and upregulates probiotics to exert anti-inflammatory effects. Pathological sections of high-dose Ume group showed mild edema in lung and stomach tissues, and high levels of TNF – α in mouse serum. This may be due to the high content of organic acids in Ume, which can be irritating to the stomach at excessive doses and cause chronic inflammation in the body. This reminds us that although Ume is a medicinal and edible substance, consuming it in high doses can also be harmful.

In summary, this study explores the mechanism of the medicinal and dietary effects of Ume from the perspective of gut microbiota, providing scientific basis for its clinical application and revealing its potential as a regulator of gut microbiota, laying a theoretical foundation for further research and development.