Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids.

The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.

Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review.

BACKGROUND: Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. OBJECTIVES: This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. METHODS: We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and ß-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. CONCLUSION: The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.

Therapeutic Effects of Valeriana jatamansi on Ulcerative Colitis: Insights into Mechanisms of Action through Metabolomics and Microbiome Analysis.

Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, which has not been completely cured in patients so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea," which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorates the symptoms and histopathological scores and reduces the production of inflammatory factors in UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis, and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.

An UPLC-MS/MS method for targeted analysis of microbial and host tryptophan metabolism after administration of polysaccharides from Atractylodes macrocephala Koidz. in ulcerative colitis mice.

Botanic polysaccharides can be metabolized by gut microbiota into short-chain fatty acids (SCFAs) to exert extensive bioactivities, yet targeted analysis of the effect of botanic polysaccharides on other gut microbial metabolites is scarcely seen. Tryptophan metabolites such as indole and indole derivatives play import roles in health and disease development. Using polysaccharides from Atractylodes macrocephala Koidz. (AMP) in treating ulcerative colitis as the example, we checked the effects of AMP on tryptophan metabolites. After examination of pharmacological effects of AMP, we established an ultra-performance liquid chromatography coupled with mass spectrometry/mass spectrometry (UPLC-MS/MS) method to simultaneously determinate the levels of 30 tryptophan metabolites and used the method to determine the levels of these metabolites in feces and plasma. The detection results showed that 12 metabolites in feces can be detected, and 17 metabolites can be detected in plasma samples. In addition, we found out that total levels of aryl hydrocarbon receptor ligands were decreased in colitis model whereas AMP treatment can increase the levels of total ligands in both feces and plasma. The results indicated that the therapeutical effect of AMP on colitis was associated with modulation of fecal and host tryptophan metabolism. This study provides new insight into the molecular mechanisms of polysaccharides that the beneficial effects of polysaccharides can be achieved by modulating microbial tryptophan metabolism in addition to SCFAs.

Ameliorative effect of Aconite aqueous extract on diarrhea is associated with modulation of the gut microbiota and bile acid metabolism.

Introduction: Aconite is a form of traditional Chinese medicine (TCM) that has been widely used to treat diarrhea for thousands of years. However, it is not clear whether the anti-diarrhea role of aconite aqueous extract (AA) is associated with regulation of the gut microbiota or with bile acid (BA) metabolism. This study aimed to confirm whether AA exerts its anti-diarrhea effects by regulating the gut microbiota and BA metabolism. Methods: The therapeutic effect of AA in a mouse model of diarrhea was measured based on analysis of body weight, fecal water content, diarrhea scores, intestinal propulsion rate, colonic pathology, and colonic immunohistochemistry. In addition, 16S rRNA high-throughput sequencing was conducted to analyze the effect of AA on the gut microbiota, and targeted metabolomics was employed to analyze the effect of AA on metabolism of BAs. Results: The results showed that treatment with AA reduced fecal water content and diarrhea scores, inhibited intestinal propulsion rate and pathological changes in the colon, and increased AQP3 and AQP4 content in the colon. In addition, AA was found to be capable of regulating the gut microbiota. Effects included increasing its richness (according to the ACE and Chao1 indices); altering the gut microbiota community structure (PCA, PCoA, and NMDS); increasing the relative abundance of norank_f_Muribaculaceae, Ruminococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, and norank_f_norank_o_Clostridia_UCG-014; and decreasing the relative abundance of Escherichia-Shigella, unclassified_f_Ruminococcaceae, Ruminococcus_torques_group, and Parasutterella. More importantly, AA significantly increased fecal TCA (a primary BA) and DCA, LCA, GDCA, dehydro-LCA, and 12-keto-LCA (secondary BAs), thus restoring BA homeostasis. Moreover, AA increased the ratios of DCA/CA, DCA/TCA, and LCA/CDCA and decreased the ratios of TLCA/LCA, GLCA/LCA, and TUDCA/UDCA. Conclusion: The anti-diarrhea effect of AA was associated with restoration of the gut microbiota and BA metabolism-related homeostasis. The results of this study provide insights into the application of AA and the treatment of diarrhea.

Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and gut microbiota metabolism.

Background: Atractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota. Methods: Acute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism. Conclusion: In conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice.

OBJECTIVE: To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice. METHODS: Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing. RESULTS: Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism. CONCLUSION: APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine.

Berberine (BBR), an isoquinoline alkaloid, has been found in many plants, such as Coptis chinensis Franch and Phellodendron chinense Schneid. Although BBR has a wide spectrum of pharmacological effects, its oral bioavailability is extremely low. In recent years, gut microbiota has emerged as a cynosure to understand the mechanisms of action of herbal compounds. Numerous studies have demonstrated that due to its low bioavailability, BBR can interact with the gut microbiota, thereby exhibiting altered pharmacological effects. However, no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects. Here, we describe the direct interactive relationships between BBR and gut microbiota, including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota. In addition, the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed. Furthermore, we provide our viewpoint on future research directions regarding BBR and gut microbiota. This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.

Interactions between polysaccharides and gut microbiota: A metabolomic and microbial review.

In recent years, gut microbiota has become a hot topic because of its important role in health and diseases. Gut microbiota can produce a series of metabolites such as short chain fatty acids (SCFAs), secondary bile acids, tryptophan and indole derivatives. Over the past decade, a large number of studies have shown that oral polysaccharides can be transported to the colon and interact with gut microbiota. However, comprehensive summarization of the interactions between polysaccharides and gut microbiota is still lacking, especially from the perspective of other gut microbiota metabolites such as trimethylamine and tryptophan. In this review, we first summarized the comprehensive interactions between polysaccharides and gut microbiota, including (1) modulation of gut microbiota composition by polysaccharides, (2) gut microbiota metabolizes polysaccharides to SCFAs, and (3) polysaccharides modulate the production of gut microbiota metabolites including trimethylamine, tryptophan, lipopolysaccharides, etc. In addition, we also discussed the indirect effects of polysaccharides on intestinal barriers and gave our perspectives on future research on polysaccharides. This review not only helps explain the underlying mechanism of polysaccharides, but also provides a reasonable reference for the better utilization of polysaccharides.

Dietary compounds in modulation of gut microbiota-derived metabolites.

Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.

Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives.

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.

Ginsenoside Rg1 Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Microbial Tryptophan Metabolism.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.

Gut microbiota, bile acids, and nature compounds.

Natural compounds (NPs) have historically made a major contribution to pharmacotherapy in various diseases and drug discovery. In the past decades, studies on gut microbiota have shown that the efficacy of NPs can be affected by the interactions between gut microbiota and NPs. On one hand, gut microbiota can metabolize NPs. On the other hand, NPs can influence the metabolism and composition of gut microbiota. Among gut microbiota metabolites, bile acids (BAs) have attracted widespread attention due to their effects on the body homeostasis and the development of diseases. Studies have also confirmed that NPs can regulate the metabolism of BAs and ultimately regulate the physiological function of the body and disease progresses. In this review, we comprehensively summarize the interactions among NPs, gut microbiota, and BAs. In addition, we also discuss the role of microbial BAs metabolism in understanding the toxicity and efficacy of NPs. Furthermore, we present personal insights into the future research directions of NPs and BAs.

Integration of Gut Microbiota and Metabolomics for Chinese Medicine Research: Opportunities and Challenges.

Chinese medicines (CM) are gaining more attentions from all over the world. However, there are a large body of questions to be answered because of the chemical complexity of CM and intricate molecular reactions within human body. In recent years, gut microbiota and metabolomics have emerged as two cynosures in deciphering the mechanisms of how our body is functioning. Since gut microbiota and host is a closely interrelated system, paying attention only to gut microbiota or metabolites may omit the interplays among CM, gut microbiota, and hosts. To systemically study these interplays, a network understanding of CM components, gut microbiota, metabolites of gut microbiota, metabolites in human body is necessary. Although there are some obstacles impeding the application of this integrative approach, the potential areas for implementation of the integrative approach is vast. These areas include, but not limited to, elucidating the mechanisms of CM at system level, screening bioactive compounds in CM, and guiding quality control of CM.

Inhibiting TGF-[Formula: see text] 1-Mediated Cellular Processes as an Effective Strategy for the Treatment of Pulmonary Fibrosis with Chinese Herbal Medicines.

Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.

Revealing the efficacy-toxicity relationship of Fuzi in treating rheumatoid arthritis by systems pharmacology.

In recent decades, herbal medicines have played more and more important roles in the healthcare system in the world because of the good efficacy. However, with the increasing use of herbal medicines, the toxicity induced by herbal medicines has become a global issue. Therefore, it is needed to investigate the mechanism behind the efficacy and toxicity of herbal medicines. In this study, using Aconiti Lateralis Radix Praeparata (Fuzi) as an example, we adopted a systems pharmacology approach to investigate the mechanism of Fuzi in treating rheumatoid arthritis and in inducing cardiac toxicity and neurotoxicity. The results showed that Fuzi has 25 bioactive compounds that act holistically on 61 targets and 27 pathways to treat rheumatoid arthritis, and modulation of inflammation state is one of the main mechanisms of Fuzi. In addition, the toxicity of Fuzi is linked to 32 compounds that act on 187 targets and 4 pathways, and the targets and pathways can directly modulate the flow of Na+, Ca2+, and K+. We also found out that non-toxic compounds such as myristic acid can act on targets of toxic compounds and therefore may influence the toxicity. The results not only reveal the efficacy and toxicity mechanism of Fuzi, but also add new concept for understanding the toxicity of herbal medicines, i.e., the compounds that are not directly toxic may influence the toxicity as well.

Aqueous extracts of Aconite promote thermogenesis in rats with hypothermia via regulating gut microbiota and bile acid metabolism.

BACKGROUND: Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer's disease, and so on. As the typical "hot" traditional Chinese medicine, Aconite has been widely used to treat cold-associated diseases for thousands of years, but its critical mechanisms for the promotion of thermogenesis are not fully resolved. Gut microbiota and its metabolites play a crucial role in maintaining energy homeostasis. Here, we investigated whether the aqueous extracts of Aconite (AA) can enhance thermogenesis through modulation of the composition and metabolism of gut microbiota in hypothermic rats. METHODS: The therapeutic effects of AA on body temperature, energy intake, and the histopathology of white adipose tissue and brown adipose tissue of hypothermic rats were assessed. Microbiota analysis based on 16 S rRNA and targeted metabolomics for bile acids (BAs) were used to evaluate the composition of gut microbiota and BAs pool. The antibiotic cocktail treatment was adopted to further confirm the relationship between the gut microbiota and the thermogenesis-promoting effects of AA. RESULTS: Our results showed a sharp drop in rectal temperature and body surface temperature in hypothermic rats. Administration of AA can significantly increase core body temperature, surface body temperature, energy intake, browning of white adipose tissue, and thermogenesis of brown adipose tissue. Importantly, these ameliorative effects of AA were accompanied by the shift of the disturbed composition of gut microbiota toward a healthier profile and the increased levels of BAs. In addition, the depletion of gut microbiota and the reduction of BAs caused by antibiotic cocktails reduced the thermogenesis-promoting effect of AA. CONCLUSIONS: Our results demonstrated that AA promoted thermogenesis in rats with hypothermia via regulating gut microbiota and BAs metabolism. Our findings can also provide a novel solution for the treatment of thermogenesis-associated diseases such as rheumatoid arthritis, obesity, and type 2 diabetes.

Gut microbiota as a target to limit toxic effects of traditional Chinese medicine: Implications for therapy.

Traditional Chinese medicines (TCMs) are medicines that are widely used in oriental countries under the guidance of ancient Chinese medicinal philosophies. With thousands of years of experiences in fighting against diseases, TCMs are gaining increasing importance in the world. Although the efficacy of TCMs is well recognized in clinic, the toxicity of TCMs has become a serious issue around the world in recent years. In general, the toxicity of TCMs is caused by the toxic medicinal compounds and contaminants in TCMs such as pesticides, herbicides, and heavy metals. Recent studies have demonstrated that gut microbiota can interact with TCMs and thus influence the toxicity of TCMs. However, there is no focused review on gut microbiota and the toxicity of TCMs. Here, we summarized the influences of the gut microbiota on the toxicity of medicinal compounds in TCMs and the corresponding mechanisms were offered. Then, we discussed the relationships between gut microbiota and the TCM contaminants. In addition, we discussed the methods of manipulating gut microbiota to reduce the toxicity of TCMs. At the end of this review, the perspectives on gut microbiota and the toxicity of TCMs were also discussed.

Polysaccharides from Atractylodes macrocephala Koidz. Ameliorate ulcerative colitis via extensive modification of gut microbiota and host metabolism.

Turbulence of gut microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids is an important factor in the development of diseases. Many polysaccharides are effective on diseases including ulcerative colitis (UC), yet most studies investigating the mechanisms of polysaccharides mainly focused on their effects on gut microbiota composition and SCFAs, and other metabolites of gut microbiota are often neglected. Here, we examined the effects of polysaccharides from Atractylodes macrocephala Koidz. (AMP) on experimental UC induced by dextran sulfate sodium (DSS) and explored underlying mechanisms of AMP by 16S rDNA-based gut microbiota analysis and untargeted fecal and plasma metabolomics. In addition, a multiscale, multifactorial network was constructed to visualize the mechanisms of AMP. The results showed that AMP significantly increased body weight and ameliorated colonic injury in DSS treated mice. AMP also partly restored the perturbed gut microbiota composition induced by DSS. Untargeted fecal and plasma metabolomics showed that AMP can not only modulate the production of SCFAs by gut microbiota, but also the ability to digest food nutrients, metabolism of amino acids and bile acids, production of cadaverine and other metabolites by hosts and gut microbiota. The study demonstrated that, in addition to SCFAs, AMP can extensively modulate the metabolism of gut microbiota and hosts to achieve the therapeutic effects. This study adds new mechanisms of polysaccharides in treating diseases.