Chlorogenic acid ameliorates intestinal inflammation via miRNA-microbe axis in db/db mice.

Chlorogenic acid improves diabetic symptoms, including inflammation, via the modulation of the gut microbiota. However, the mechanism by which the microbiota is regulated by chlorogenic acid remains unknown. In this study, we firstly explored the effects of chlorogenic acid on diabetic symptoms, colonic inflammation, microbiota composition, and microRNA (miRNA) expression in db/db mice. The results showed that chlorogenic acid decreased body weight, improved glucose tolerance and intestinal inflammation, altered gut microbiota composition, and upregulated the expression level of five miRNAs, including miRNA-668-3p, miRNA-467d-5p, miRNA-129-1-3p, miRNA-770-3p, and miRNA-666-5p in the colonic content. Interestingly, the levels of these five miRNAs were positively correlated with the abundance of Lactobacillus johnsonii. We then found that miRNA-129-1-3p and miRNA-666-5p promoted the growth of L. johnsonii. Importantly, miRNA-129-1-3p mimicked the effects of chlorogenic acid on diabetic symptoms and colonic inflammation in db/db mice. Furthermore, L. johnsonii exerted beneficial effects on db/db mice similar to those of chlorogenic acid. In conclusion, chlorogenic acid regulated the gut microbiota composition via affecting miRNA expression and ameliorated intestinal inflammation via the miRNA-microbe axis in db/db mice.

The process of hypertension induced by high-salt diet: Association with interactions between intestinal mucosal microbiota, and chronic low-grade inflammation, end-organ damage.

Inflammation and immunity play a major role in the development of hypertension, and a potential correlation between host mucosal immunity and inflammatory response regulation. We explored the changes of intestinal mucosal microbiota in hypertensive rats induced by high-salt diet and the potential link between the intestinal mucosal microbiota and inflammation in rats. Therefore, we used PacBio (Pacific Bioscience) SMRT sequencing technology to determine the structure of intestinal mucosal microbiota, used enzyme-linked immunosorbent assay (ELISA) to determined the proinflammatory cytokines and hormones associated with hypertension in serum, and used histopathology methods to observe the kidney and vascular structure. We performed a potential association analysis between intestinal mucosal characteristic bacteria and significantly different blood cytokines in hypertensive rats induced by high-salt. The results showed that the kidney and vascular structures of hypertensive rats induced by high salt were damaged, the serum concentration of necrosis factor-α (TNF-α), angiotensin II (AngII), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly increased (p < 0.05), and the coefficient of immune organ spleen was significantly changed (p < 0.05), but there was no significant change in serum lipids (p > 0.05). From the perspective of gut microbiota, high-salt diet leads to significant changes in intestinal mucosal microbiota. Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were the dominant differential bacteria in intestinal mucosal, with the AUC (area under curve) value of Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were 1 and 0.875 according to ROC (receiver operating characteristic) analysis. Correlation analysis showed that Bifidobacterium animalis subsp. was correlated with IL-6, IL-8, TNF-α, and Ang II. Based on our results, we can speculated that high salt diet mediated chronic low-grade inflammation through inhibited the growth of Bifidobacterium animalis subsp. in intestinal mucosa and caused end-organ damage, which leads to hypertension.

Chlorogenic acid improves glucose tolerance, lipid metabolism, inflammation and microbiota composition in diabetic db/db mice.

Introduction: Chronic and acute chlorogenic acid (CGA) can improve glucose tolerance (GT) and insulin sensitivity (IS). However, whether acute administration of CGA has beneficial effects on hepatic lipid metabolism and cecal microbiota composition remains unclear. Methods: In the current study, diabetic db/db mice were administered CGA or metformin, and db/m mice were used as controls to explore the effects of CGA on hepatic lipid metabolism, including fatty acid oxidation and transportation and triglyceride (TG) lipolysis and synthesis. Moreover, alterations in the inflammatory response and oxidative stress in the liver and gut microbe composition were evaluated. Results: The results showed that CGA decreased body weight and improved glucose tolerance and insulin resistance, and these effects were similar to those of metformin. CGA decreased hepatic lipid content by increasing the expression of CPT1a (carnitine palmitoyltransferase 1a), ACOX1 (Acyl-CoA oxidase 1), ATGL (adipose triglyceride lipase), and HSL (hormone-sensitive lipase) and decreasing that of MGAT1 (monoacylglycerol O-acyltransferase 1), DGAT1 (diacylglycerol O-acyltransferase), DGAT2, CD36, and FATP4 (fatty acid transport protein 4). Additionally, CGA restored the expression of inflammatory genes, including TNF-α (tumor necrosis factor-alpha), IL-1ß (interleukin-1beta), IL-6, and IL-10, and genes encoding antioxidant enzymes, including SOD1 (superoxide dismutases 1), SOD2 (superoxide dismutases 2), and GPX1 (glutathione peroxidase 1). Furthermore, CGA improved the bacterial alpha and beta diversity in the cecum. Moreover, CGA recovered the abundance of the phylum Bacteroidetes and the genera Lactobacillus, Blautia, and Enterococcus. Discussion: CGA can improve the antidiabetic effects, and microbes may critically mediate these beneficial effects.

"Liver-gut" axis: A target of traditional Chinese medicine for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) occurs when fat accumulates in the liver even without excessive alcohol intake. Among the current therapeutic approaches for NAFLD, lifestyle modification with dietary changes and regular exercise is the mainstay treatment. With the rise of intestinal microecology, regulation of the "liver-gut" axis can be an effective treatment for NAFLD. This review aimed to assess the modulation of the liver-gut microbiota axis with traditional Chinese medicine (TCM) as a therapeutic approach to NAFLD and further explored its application in the newly discovered therapeutic avenues beyond NAFLD treatment.

Intestinal microbiota-mediated dietary fiber bioavailability.

Dietary fiber is a kind of carbohydrate that cannot be digested and absorbed by the small intestine of humans but can be fermented in all or part of the large intestine and is significantly healthy for the human body. With the improvement in living standards, people pay more attention to their intestinal health, and the relationship between dietary fiber, intestinal microecological and body physiological balances, and their molecular connection mechanism has become a research hot spot. In this study, we reviewed its mediated bioavailability to provide a basis for the rational classification of dietary fiber and to guide the development of new healthy foods and the deep processing of food and its application.

Study on Baohe Pills Regulating Intestinal Microecology and Treating Diarrhea of High-Fat and High-Protein Diet Mice.

Objective: To investigate the effects of Baohe pills on intestinal microorganisms and enzyme activities in mice with a high-fat and high-protein diet. Methods: 45 KM male mice were randomly divided into the control group, the high-fat and high-protein diet group, and the Baohe pill intervention group. The mice in the high-fat and high-protein diet group and the Baohe pill intervention group were fed with the self-made high-fat and high-protein diet as the sole food source of the mice, and the mice in the control group were fed with the normal diet. Starting from the 7th day of the feed intervention, mice in the Baohe pill intervention group were given 0.28 g/mL of Baohe pill decoction twice a day at the dose of 6.67 g/(kg·day), each time of 0.35 mL for 6 days. Mice in the control group and the high-fat and high-protein diet group were given the same amount of distilled water by gavage. The general state of mice in each group was observed, and the changes of intestinal microorganisms and intestinal enzyme activities were analyzed by culturable microorganism technology and intestinal functional enzyme detection technology. Results: The excrement of mice fed with a high-fat and high-protein diet was relatively thin and wet, and the Baohe pill intervention could not improve the symptoms well. In the high-fat and high-protein diet group, the number of bacteria, Escherichia coli, Lactobacillus, and Bifidobacterium, was significantly lower than that in the control group (P < 0.01). Baohe pills could obviously increase the high-fat, high-protein diet for the number of culturable microorganisms in mice, the total number of bacteria, and the number of Bifidobacteria in the most significant (P < 0.01), but the number of bacteria, Escherichia coli, and the Lactobacillus are still significantly lower than the control group (P < 0.01). In terms of enzyme activity, both contents and mucosa, the Baohe pill could improve the activities of amylase, protease, sucrase, and lactase in high-fat and high-protein diet mice, which were significantly different from the control group (P < 0.05). In terms of microbial activity, the intestinal contents of high-fat and high-protein mice were lower than those of the control group, while the intestinal mucosa was higher than that of the control group, but the difference was not significant (P > 0.05). Baohe pills could improve the intestinal contents and intestinal mucosal microbial activity of mice, and the difference was significant in the high-fat and high-protein diet group (P < 0.05). Discussion. A high-fat and high-protein diet can destroy the physiological balance of the body, which is mainly reflected in the disturbance of intestinal flora and the decrease of some enzyme activities and microbial activity. Baohe pills can restore the number of intestinal flora to a certain extent and improve the activities of various digestive enzymes including protease and amylase.

Bacterial diversity in intestinal mucosa of mice fed with Dendrobium officinale and high-fat diet.

This study aimed to explore the effect of Dendrobium officinale (DO) on the diversity of intestinal mucosal flora in high-fat diet mice and provided an experimental basis for the development and research of DO and its series products. Twenty-four mice were randomly assigned to four equal groups of six mice, namely the control (bcm) group, model (bmm) group, Dendrobium officinale (bdm) group, and positive control (bjm) group. Mice in the bdm group were administrated at the dose of 2.37 g·kg-1·days-1, and those in bjm group were given the Lipid-lowering decoction at the concentration of 1.19 g·kg-1·days-1, and sterile water was used as a placebo control twice a day for 40 consecutive days. We measured the dynamic weight changes and intestinal mucosal flora changes in mice. The analysis showed that DO had a regulatory effect on weight change induced by a high-fat diet in mice. DO could also regulate the changes in the diversity of the intestinal mucosa of mice, which was specifically reflected in the changes of Chao 1, ACE, Shannon and Simpson index. The sample information of the bdm group was relatively concentrated, but the distance from the bmm group was relatively scattered. The relative abundance results showed dominant bacteria phylum (such as Bacteroidetes, Actinobacteria, Verrucomicrobia) and bacterial genus (such as Bifidobacterium, Ruminococcus, Ochrobactrum) in the intestinal mucosa of the four groups. And significant differences in the major microbiota between the bdm and bjm groups. In addition, DO changed the carbohydrate, energy, and amino acid metabolism of intestinal mucosal flora. To sum up, DO has a regulatory effect on weight change induced by high-fat diet in mice and can improve the diversity of intestinal mucosal flora, promote the abundance of Ochrobactrum, inhibit the abundance of Bifidobacterium and Ruminococcus, and influence the intestinal flora to positively affect high-fat diet-induced negative effects in mice.

Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.

Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.

Use of Chlorogenic Acid against Diabetes Mellitus and Its Complications.

Chlorogenic acid (CA) is a phenolic compound commonly found in human plant-based diets. CA is the main component of many traditional Chinese medicine preparations, and in recent years, it has been found to have hypoglycemic, hypolipidemic, anti-inflammatory, antioxidant, and other pharmacological properties. Specifically, CA relieves the effects of, and prevents, diabetes mellitus (DM). In addition, CA is also beneficial against complications arising from DM, such as diabetic nephropathy (DN), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Herein, we review the use of CA in the prevention and treatment of DM and its complications, providing a background for further research and medical uses.

Bacterial diversity in the intestinal mucosa of mice fed with Asparagus extract under high-fat diet condition.

The purpose of this study is to determine the effect of Asparagus on bacterial diversity in the intestinal mucosa of mice fed with high-fat diet, thus providing theoretical basis for the development and research of Asparagus products. Twelve healthy male Kunming mice and twelve healthy female Kunming mice were chosen and randomly divided into normal group, model group, Asparagus group, and lipid-lowering decoction group, with six mice in each group. After establishing the models of mice fed with high-fat diet through feeding with high-fat diet, the mice in the Asparagus group were gavaged with Asparagus juice, those in the lipid-lowering decoction group were gavaged with lipid-lowering decoction, and those in the normal group and high-fat diet group were gavaged with the equal amount of distilled water. Intestinal mucosa from the jejunum to ileum were collected, and DNA was extracted from each mice. The characteristics of the intestinal microbial species were analyzed by PacBio Sequel-based 16S rRNA sequencing. Result showed that the total OTU reached 1559 in the normal group, 1750 in the high-fat diet group, 1795 in the lipid-Lowering decoction group, and 1635 in the Asparagus group, which indicated that the Asparagus juice could inhibit the total OUT of intestinal bacteria. The analysis on sample community diversity indicated that the richness, diversity, richness estimation, and diversity in the Asparagus Group, lipid-lowering decoction group, and normal group were lower than those in the high-fat diet group. Bacteriophyta classification analysis indicated that the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria in the Asparagus group was between that in the high-fat diet group and normal group. In conclusion, Asparagus can affect the diversity of bacteria in the intestinal mucosa of mice fed with high-fat diet, and achieve a lipid-lowering effect by regulating the intestinal microecology of mice fed with high-fat diet.