This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.
Animals ; Anti-Bacterial Agents/adverse effects* ; Diarrhea/drug therapy* ; Gastrointestinal Microbiome ; Ginger ; Plant Extracts ; Rats ; Rhizome

Traditional Chinese medicine boasts aunique theoretical system and rich practical experience. However, traditional Chinese medicine has an unclear material basis, vague pharmacological mechanism, and potential toxicity, which is the key factor to hinder its modernization and wide application. Therefore, when the physico-chemical analysis of chemical components of traditional Chinese medicine is insufficient to reflect the characteristics and mechanisms, the multi-target biological system correlation analysis in conformity to the holistic view of the basic theory of traditional Chinese medicine has gradually attracted wide attention. Specifically, bile acids, as an important endogenous metabolite in the body, play an important role in regulating digestion, absorption and metabolism of nutrients, and greatly impact the health. In recent years, a number of studies have been made on the metabolism pathway of bile acids and their important regulatory effects in body metabolism, making bile acids as a significant target of traditional Chinese medicine on the body. In view of this, based on bile acid metabolism, the paper reviewed the biological functions of bile acids in regulating body metabolism and its interaction with intestinal microbiota, providing a basis for exploring the connotation of bile acid metabolism changes under physiological/pathological conditions of the body. The study progress of bile acid metabolism in traditional Chinese medicine efficacy/toxic mechanism is further reviewed, which provides a basis for exploring the efficacy and hepatotoxicity mechanism of traditional Chinese medicine with bile acid as a biomarker, thereby laying a foundation for the clinical safety of traditional Chinese medicine.
Bile Acids and Salts ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; Gastrointestinal Microbiome ; Humans ; Medicine, Chinese Traditional

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.
Animals ; Bacteria ; classification ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Metabolomics ; Rats ; Tandem Mass Spectrometry

The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.
Animals ; Arsenic Trioxide/pharmacology* ; Arsenicals/pharmacology* ; Bacteria/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Sulfides/pharmacology*

This study was designed to investigate the effect of Gegen Qinlian(GGQL) Decoction and its different compatibility groups on gut microbiota in rats with acute enteritis, and to explore the efficacy of GGQL Decoction in improving acute enteritis and gut microbiota. Male SD rats were randomly divided into control group, model group, positive control group(SASP), GGQL decoction group, Glycyrrhizae-free group(QGC), Puerariae-free group(QGG), Qinlian-free group(QQL), and Qinlian group(QL). The pathological sections and detection indexes of the rats were observed before and after modeling and administration. After 7 days of administration, fecal samples from 24 rats were collected and Illumina Miseq platform was used for high-throughput sequencing. From the anti-inflammatory and pharmacodynamic indicators, the effect was the most obvious in GGQL Decoction group, QGC group, QGG group and QL group(P<0.05). The alpha diversity and beta diversity showed that there were significant differences in the composition of intestinal flora in each group. As compared with the model group, the increased abundance and diversity of the flora caused by acute inflammation could be down-regulated in all groups except QQL group(P<0.05). The differential bacteria were explored by using LEfSe analysis, and the results showed that Bifidobacterium and other beneficial bacteria only appeared in the normal group. As compared with the normal group, Lactobacillus was significantly reduced(P<0.01), and Bacteroides, Flavonifractor and Clostridium_sensu_stricto_1 were up-regulated in model group(P<0.05, P<0.01). As compared with the model group, the number of Akkermansia was significantly increased(P<0.05), and the number of Clostridium_sensu_stricto_1 associated with intestinal inflammatory diseases was decreased in the GGQL Decoction group, QGC group and QL group. QGC group and QQL group caused the up-regulation of Ruminococcaceae and induced enrichment of Desulfovibrio which could lead to colon cell toxicity; QGG group caused the up-regulation of Proteobacteria and Burkhonderiales. The study suggests that the GGQL Decoction may play a role in the treatment of acute enteritis partially through improving the intestinal barrier, regulating the immune response and the structure of gut microbiota.
Animals ; Bacteria/classification* ; Drugs, Chinese Herbal/pharmacology* ; Enteritis/drug therapy* ; Feces ; Gastrointestinal Microbiome/drug effects* ; High-Throughput Nucleotide Sequencing ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
Animals ; Bacteria ; classification ; genetics ; isolation & purification ; metabolism ; Butyrates ; metabolism ; Fatty Liver ; drug therapy ; Fungal Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; genetics ; Hyperglycemia ; drug therapy ; Hyperlipidemias ; drug therapy ; Intestines ; drug effects ; microbiology ; Male ; Metabolic Syndrome ; drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia ; chemistry

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; radiotherapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; pharmacology

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.
Animals ; Croton ; chemistry ; Diuretics ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Glycyrrhiza ; chemistry ; Intestines ; Mice ; Plant Roots ; chemistry ; Seeds ; chemistry