The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.

Panacis Quinquefolii Radix, a valued herb in traditional Chinese medicine, is frequently prescribed for its immunomodulatory effects and its potential to improve cardiovascular function. Recently, there is an increasing amount of research on ginseng polysaccharides, due to their variety of pharmacological activities, including anti-inflammatory, hepatoprotective, cardiovascular protective, and the improvement of intestinal function.

This study investigates the efficacy of Panacis Quinquefolii Radix polysaccharides in alleviating cardiovascular diseases and to achieve the high-value utilization of ginseng by-products.

A pectic polysaccharide named XYSJY2-2 was extracted with hot water from stems and leaves of Panacis Quinquefolii Radix and further isolated by a DEAE Sepharose Fast Flow column and a Sephacry S-100 column. The structural characteristics of XYSJY2-2 was determined by monosaccharide composition, IR, NMR, and methylation analysis. The cardioprotective activity of this polysaccharide was evaluated in vitro and in vivo. With a relative molecular weight of 5.1 kDa, XYSJY2-2 is a type I rhamnogalacturonan featuring a core backbone made up of alternately linked rhamnose and galacturonic acid.

XYSJY2-2 effectively alleviated myocardial hypertrophy and remodeling induced by Ang II and TAC in vivo and in vitro, partly due to suppressing Nppa and Nppb expression.

A pectic polysaccharide from stems and leaves of Panacis Quinquefolii Radix has the potential to alleviate cardiovascular disease.

Cyclophosphamide (CTX) is a widely used anticancer drug in clinical practice; however, its administration can lead to gastrointestinal damage and immune suppression. Lactobacillus murinus (L. murinus) has been shown to regulate immune cell activity and protect the gastrointestinal system, showing potential application as a functional food. The objective of this study was to investigate the effects of L. murinus ZNL-13 on CTX-induced intestinal mucosal injury and gut microbiota in mice. The results demonstrated that L. murinus ZNL-13 significantly alleviated weight loss and intestinal pathological damage. Moreover, in CTX-induced intestinal injury mice, L. murinus ZNL-13 enhanced the release of immune factors, suppressed cell apoptosis, and protected the intestinal mucosal barrier. Additionally, it activated the TLR4/NF-κB pathway, thereby promoting immune cell activity. Furthermore, L. murinus ZNL-13 contributed to the restoration of gut microbial homeostasis by increasing the relative abundance of short-chain fatty acid-producing bacteria. Taken together, this investigation highlights the potential of L. murinus ZNL-13 in protecting the intestinal barrier and enhancing immune function while laying the groundwork for its development as a novel probiotic and functional food.

Probiotic fermentation can promote the release of more effective components from traditional Chinese medicines (TCMs). Astragalus membranaceus (Fisch.) Bunge (A. membranaceus) and Raphani Semen are TCMs that have gained attention for their immunoenhancing activities. This study aimed to investigate the effects and underlying mechanisms of probiotic-fermented A. membranaceus and Raphani Semen (PROAS) in cyclophosphamide (CTX)-induced immunocompromised mice. Changes in the composition of A. membranaceus and Raphani Semen after fermentation by probiotic strains, including Bifidobacterium longum SD5219, Lactobacillus fermentum NCIMB5221, and Lactobacillus paracasei SD5219, were identified using high-performance liquid chromatography. The immunostimulatory effects and mechanisms of PROAS were evaluated in immunosuppressed mice 3 and 7 days after CTX treatment. Probiotic fermentation of TCMs resulted in changes in major bioactive components. PROAS supplementation effectively restored intestinal integrity in CTX-treated mice by upregulating the mRNA expression of the tight junction proteins. PROAS significantly ameliorated the reduction in the spleen index and number of B lymphocytes caused by CTX treatment and regulated the secretion of cytokines in serum and colon tissues. PROAS administration modulated gut microbial dysbiosis and short-chain fatty acid (SCFA) content in CTX-treated mice. These results suggest that PROAS enhances B lymphocyte function by increasing the regulation of intestinal microbiota to produce high levels of SCFA, repairs the intestinal barrier damage induced by CTX, and promotes intestinal mucosal immunity.

Black ginseng (BG), a novel manufactured ginseng product, is gaining market attention due to its high polarity and similar structure constituents. In this work, the primary constituents of Panax quinquefolium L. BG, including ginsenosides and derivatives, were separated using high-speed counter-current chromatography in conjunction with evaporative light scattering detection by recycling and consecutive mode, as well as the elution-extrusion method for continuous sample loading. Sample loading and mobile phase ratios were among the optimized primary separation parameters. Nine compounds, including ginsenoside Rg6 (1), 22(E)-ginsenoside F4 (2), ginsenoside Rk3 (3), ginsenoside Rh4 (4), ginsenoside Rg3 (5), 20(R)-ginsenoside Rg3 (6), (3R,9R,10R)-panaxytriol (7), ginsenoside Rk1 (8), and ginsenoside Rg5 (9), were ultimately effectively isolated. Mass spectrometry and nuclear magnetic resonance spectrometry were used to investigate the structures. Based on our research, the developed process was a successful way to separate the primary ingredients from BG. Purification of additional comparable high-polarity chemicals from complicated natural products might be accomplished using the stated methodology.

Pectin is an acidic heteropolysaccharide with natural, green, and inexpensive characteristics. Compared to polysaccharides, oligosaccharides are more easily utilized by the body, and the physiological function of hawthorn pectin oligosaccharides (POS) may vary depending on their degree of polymerization (DP). Therefore, we mainly studied the effects of hawthorn pectin (HP) and POS with different DP on gut microbiota disorders induced by high-fat diet (HFD). HP and POS both improved weight gain, dyslipidemia, and glucose homeostasis caused by HFD, and increased serum GLP-1 levels. Meanwhile, the increased expression of Gcg and Pcsk1 genes in the ileum of the treatment group further confirmed this result. In addition, HP and POS reduced certain opportunistic pathogens, while restoring the richness and diversity of the gut microbiota. Meanwhile, HP and POS can improve intestinal barrier dysfunction by increasing the claudin-1, occludin, ZO-1, and MUC2 genes. Furthermore, fecal metabolomics suggests that POS may enhance linoleic acid synthesis and improve lipid metabolism by upregulating 9,10-DHOME ((12Z)-9,10-dihydroxyoctadec-12-enoic acid), while HP cannot. Overall, the research results indicate that both HP and POS can improve the weight phenotype changes, gut microbiota disruption, and metabolites changes caused by HFD. Particularly, POS has a better effect than HP, and there are differences in the improvement effect of POS with different DP, among which POS with DP 5 has the most significant improvement effect. This discovery enhances a deeper comprehension of the biological activity of different POS, providing an important basis for further optimizing the application of POS as a functional food.

In this editorial, we discuss the findings reported by Wang et al in the latest issue of the World Journal of Gastrointestinal Oncology. Various research methodologies, including microbiome analysis, assert that the Tzu-Chi Cancer-Antagonizing and Life-Protecting II Decoction of Chinese herbal compounds mitigates inflammatory responses by inhibiting the NF-κB signaling pathway. This action helps maintain the dynamic equilibrium of the intestinal microecology and lessens chemotherapy-induced gastrointestinal damage. The efficacy of these compounds is intimately linked to the composition of intestinal microbes. These compounds regulate intestinal microecology by virtue of their specific compatibility and effectiveness, thereby enhancing the overall therapeutic outcomes of cancer chemotherapy. Nonetheless, the exact mechanisms underlying these effects warrant further investigation. Multi-omics technologies offer a systematic approach to elucidate the mechanisms and effectiveness of Chinese herbal compounds in vivo. This manuscript reviews the application of multi-omics technologies to Chinese herbal compounds and explores their potential role in modulating the gastrointestinal microenvironment following cancer chemotherapy, thus providing a theoretical foundation for their continued use in adjunct cancer treatment.

Since the development of immune checkpoint inhibitors (ICIs), immunotherapy has been widely used as a novel cancer treatment. However, the efficacy of tumor immunotherapy is largely dependent on the tumor microenvironment (TME). The high degree of heterogeneity within TME remains a major obstacle to acquire satisfactory therapeutic. Emerging studies suggest that gut microbiota is becoming an important regulator of TME. Polysaccharides as tumor immunotherapeutic agents or immune adjuvants not only exhibit antitumor activity by targeting gut microbiota, but also expand their role in the tumor immunotherapy by remodeling TME. To date, the mechanism by which polysaccharides targeting TME for tumor prevention via gut microbiota has not been deeply investigated. In this review, recent advances in the regulation of TME by polysaccharides through gut microbiota were systematically outlined, and the challenges and possible solutions in the clinical application of TME-targeted polysaccharides were discussed. Exploring the relationship between polysaccharides and TME from the perspective of gut microbiota may provide new ideas for the application of polysaccharides in tumor immunotherapy. This is a new area with major challenges that deserve further exploration.

Mitoxantrone (MTX) is largely restricted in clinical usage due to its significant cardiotoxicity. Multiple studies have shown that an imbalance in the gut-heart axis plays an important role in the development of cardiovascular disease (CVD). We aim to explore the possible correlations between gut microbiota (GM) compositions and cardiometabolic (CM) disorder in MTX-triggered cardiotoxicity mice.

MTX cumulative dose of 6 mg/kg was administered to healthy Kunming male mice to trigger cardiotoxicity, with 1 mg/kg twice weekly for a duration of 3 weeks. Plasma CK-MB and LDH levels were determined, and the heart tissue histopathology was assessed, followed by utilizing an integrated liquid chromatography-mass spectrometry (LC-MS)-based heart metabolomics study alongside the 16S ribosomal RNA (rRNA) sequencing method to assess MTX impact on GM and CM profiles in mice, establishing associations between GM and CM profiles through the Pearson correlation coefficient calculation.

MTX caused CK-MB and LDH level elevations and cardiotoxicity in our mouse model. MTX primarily affected the processes of protein digestion and absorption, mineral absorption, membrane transport, production of aminoacyl-transfer RNA (tRNA), metabolism of nucleotides, lipids, and amino acids, as well as autophagy. Additionally, MTX increased Romboutsia, Enterococcus, and Turicibacter abundances and lowered norank_f__Muribaculaceae, Alistipes, Odoribacter, norank_f__Lachnospiraceae, norank_f__Ruminococcaceae, norank_f__Oscillospiraceae, unclassified_f__Ruminococcaceae, NK4A214_group, Colidextribacter, norank_f__norank_o__Clostridia_vadinBB60_group, Rikenella, and Anaerotruncus abundances. The correlation analyses showcased variations in the abundance of diverse flora, such as Romboutsia, Enterococcus, Turicibacter, and norank_f__Muribaculaceae, which were related to MTX-induced cardiac injury.

Our study supports the claim that MTX provokes cardiotoxicity by modifying CM and GM profiles. Our results offer new possibilities for controlling MTX-triggered cardiotoxicity.

Background: Shenlian (SL) decoction, a renowned traditional Chinese formula for diabetes mellitus, has also been employed to treat intestinal disorders. Previous studies have demonstrated the efficacy of SL decoction in regulating blood glucose and intestinal bacteria. Nevertheless, further analysis is required to elucidate the mechanistic link between SL decoction-mediated improvement of intestinal function and treatment of Type 2 diabetes mellitus (T2DM). Methods: Firstly, the active ingredients of SL decoction were sourced from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, with putative targets of active ingredients being predicted using the same database. Secondly, the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were employed to screen the aforementioned targets that act on T2DM, and protein-protein interaction (PPI) networks were constructed in accordance with the results. Thirdly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), which resulted in a comprehensive analysis of the association between SL decoction for the treatment of T2DM and the modulation of intestinal functions. Finally, the effect of the SL decoction on predicted lipopolysaccharide (LPS)-related targets, as well as intestinal function markers, was validated through in vivo experimentation. Results: A total of 36 active ingredients and 145 potential targets of SL decoction were predicted. GO enrichment analysis indicated that the principal biological processes by which the SL decoction acted against T2DM were responses to LPSs, while KEGG enrichment analysis identified the nuclear factor kappa B (NF-κB) signaling pathway and toll-like receptor signaling pathway as the key pathways involved. The in vivo experiments showed that SL decoction improved glycolipid metabolism indexes, inflammatory factor levels, and LPS levels in db/db mice. The immunohistochemical results demonstrated that the SL decoction restored the expression of Occludin, Claudin-1, and ZO-1 in the intestine and inhibited the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MYD88), and NF-κB in both the intestine and pancreas. Furthermore, it may influence the levels of short-chain fatty acids (SCFAs) in feces. Conclusions: This research investigated the multigene pharmacological mechanism of SL decoction against T2DM using network pharmacology and in vivo experiments. SL decoction treatment of T2DM may reverse inflammation by inhibiting LPS-related pathway activation and improving intestinal function.

Ginseng may improve the myelosuppression and intestinal microbiota disorder induced by cyclophosphamide (CY); however, the effect of ginseng components on hematopoietic stem cell (HSC) damage remains largely unexplored. The present study aimed to assess the protective effect of ginseng extract (GE), total ginsenosides (TG) and total polysaccharides (TP) from ginseng on the intestinal microflora and HSCs of model mice. In the present study, a mouse model of HSC damage induced by CY was constructed, intestinal microflora of fecal samples were sequenced using the 16S ribosomal RNA (rRNA) sequencing techniques, the differentially expressed genes (DEGs) of HSCs were analyzed using high‑throughput RNA‑sequencing, cell apoptosis and erythroid differentiation were detected using flow cytometry and the blood cell parameters were analyzed using a hematology analyzer. Analysis of the 16S rRNA in fecal samples showed that GE, TG and TP improved an imbalanced intestinal microflora, where the relative abundance of Lactobacillus intestinalis had a positive correlation with ginsenosides content. Specifically, TP significantly increased the expression of low‑abundance microflora. Transcriptomic analysis results revealed 2,250, 3,432 and 261 DEGs in the GE, TG and TP groups compared with those in the Model group, respectively. In the expression analysis of DEGs, both TG and GE were found to markedly increase the expression levels of Klf4, Hhex, Pbx1, Kmt2a, Mecom, Zc3h12a, Zbtb16, Lilr4b, Flt3 and Klf13. Furthermore, TG inhibited the apoptosis of HSCs by increasing the expression levels of Bcl2 and Mcl1, whilst decreasing the expression of Bax. By contrast, GE inhibited the apoptosis of HSCs by reducing the expression of Bax and Bad. Regarding erythroid differentiation and blood cell parameters, GE was found to significantly increase the expression of TER‑119. In addition, GE and TG improved all blood cell parameters, including the count of white blood cells, neutrophils (NEUT), lymphocytes (LYMPH), red blood cells (RBC), hemoglobin (HGB) and reticulocyte and platelets (PLT), whereas TP could only improve the counts of LYMPH, RBC, HGB and PLT. The improvement effect of GE and TG on WBC, NEUT and Ret was superior to TP. In conclusion, TG may protect the hematopoiesis function of HSCs in a CY‑induced mouse model of HSC damage, followed by GE. However, TP did not appear to improve HSC damage. Ginsenosides may therefore be considered essential ingredients in GE when protecting HSCs against damage. GE and TG exerted their protective effects on HSCs by inhibiting the apoptosis of HSCs whilst improving the imbalance of intestinal microflora.

Aflatoxin B1 (AFB1) has been recognized as a serious health risk for ruminant animals. From a molecular perspective, indole-3-acid (IAA) possesses the potential to enhance the removal of AFB1 by rumen microbiota. Therefore, this study aims to investigate the impact of different concentrations of IAA on the removal of AFB1 by rumen microbiota using an in vitro technique. Experiment 1: interaction between AFB1 and rumen fermentation. Experiment 2: The study used a randomized design with five IAA levels (0, 15, 150, 1,500, and 7,500 mg/kg) to examine the effect of IAA on AFB1 removal and its impact on rumen fermentation. The results showed: (1) the content of AFB1 gradually decreased, removal rate of up to 75.73% after 24 h. AFB1 exposure altered the rumen fermentation pattern, with significantly decreased in the acetic acid/propionic acid ratio (p < 0.05). It significantly reduced the relative proportions of R. amylophilus, P. ruminicola, and F. succinogenes (p < 0.05). (2) As the content of IAA increased, AFB1 exposure decreased. A total of 15 and 150 mg/kg IAA significantly mitigated the negative impact of AFB1 on key rumen bacteria (R. amylophilus, P. ruminicola and F. succinogenes), increased acetate levels and acetate/propionate ratio (p < 0.05). However, 1,500 mg/kg IAA lowered levels of propionate and isovalerate, adversely affected enzyme activities (pectinase, xylan and Carboxymethyl-cellulase) and relative proportions of microbiota (R. flavefaciens, P. ruminicola and F. succinogenes). In conclusion, IAA significantly removed AFB1, and in the range of 150 mg/kg of IAA reduced the negative effects of AFB1 on in vitro fermentation characteristics and fermentation end-products.

As a typical medicinal food homology species, Chinese herbal medicine Astragali radix (AR) has been widely used to regulate the human immune system worldwide. However, the human immunomodulation of AR and its corresponding mechanisms remain unclear.

First, following a fortnight successive AR administration, the changes in immune cytokines and immune cells from 20 healthy human subjects were used as immune indicators to characterize the immunomodulatory effects of AR. Subsequently, ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) based lipidomics and metabolomics analysis was performed on human serum, urine, and feces samples to investigate the changes in metabolic profiles. Then, 16S rRNA gene sequencing of feces samples was adopted for the changes of human gut microbiota. Finally, correlation analysis was conducted on the gut microbiome, metabolome/lipidome data, and immune indicators.

AR displayed good safety in clinical use and posed a minor impact on gut microbiota major genera, global metabolic profiles, and immune cells. Meanwhile, AR could significantly up-regulate anti-inflammatory cytokines, down-regulate serum creatinine and pro-inflammatory cytokines, promote the anabolism of arginine, glycerolipid, sphingolipid, and purine, and the catabolism of phenylalanine and glycerophospholipid. Moreover, these AR-induced changes were closely correlated with significantly decreased Granulicatella, slightly higher Bifidobacterium, Ruminococcus, and Subdoligranulum, and slightly lower Blautia.

The study clearly demonstrated that AR could modulate the human immune, by modifying the metabolism of amino acids, lipids, and purines in a microbiota-related way. Trial registration ChiCTR, ChiCTR2100054765. Registered 26 December 2021-Prospectively registered, https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2100054765.

The gut microbiota plays a crucial role in maintaining homeostasis in the human gastrointestinal tract. Numerous studies have shown a strong association between the gut microbiota and the emergence and progression of various diseases. Leukemia is one of the most common hematologic malignancies. Although standardized protocols and expert consensus have been developed for routine diagnosis and treatment, limitations remain due to individual differences. Nevertheless, a large number of studies have established a link between the gut microbiota and leukemia, with disturbances in the gut microbiota directly or indirectly affecting the development of leukemia. However, the causal relationship between the two remains unclear, and studying and exploring the causal relationship may open up entirely new avenues and protocols for use in the prevention and/or treatment of leukemia, offering new insights into diagnosis and treatment. In this review, the intricate relationship between the gut microbiota and leukemia is explored in depth, including causal associations, metabolite effects, therapeutic applications, and complications. Based on the characteristics of the gut microbiota, the future applications and prospects of gut microbiota are discussed to provide useful information for clinical treatment of leukemia.

Probiotics play a crucial role in regulating the gut microbiota and enhancing immune response. Oral administration of probiotics modulates intestinal microbiota composition and immune homeostasis. In this study, we investigated the immunoregulatory effect of Lacticaseibacillus rhamnosus LRa05 on cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that oral administration of LRa05 reduced weight loss, restored immune organ indices, and maintained the structural integrity of the intestinal tissue in CTX-treated mice. Moreover, oral administration of LRa05 exhibited immune-modulating properties by promoting the secretion of cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-10, and secretory immunoglobulin A) in serum. Moreover, the analysis of 16S rRNA amplicon sequencing revealed that LRa05 increased gut microbiota diversity and regulated its composition. In detail, LRa05 intervention restored the Firmicutes/Bacteroidota ratio and significantly increased the relative abundance of Lachnospiraceae_NK4A136_group, Oscillibacter, Alloprevotella, Parasutterella, and Roseburia in immunocompromised mice. Conversely, the abundances of Helicobacter, Bacteroides, and unclassified_Desulfovibrionaceae were significantly decreased after administration of LRa05. Based on these findings, orally administered LRa05 could effectively maintain intestinal microbiota homeostasis and regulate immunity, suggesting the potential of L. rhamnosus LRa05 as a candidate probiotic strain in the application of dietary supplement. PRACTICAL APPLICATION: Supplement with L. rhamnosus LRa05 can improve immunity, regulate gut microbiota and promote body health.

Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.

Plants from the Panax genus have significant medicinal and nutritional benefits. Many Panax species are traditionally used in Chinese medicine and have gained popularity as food and health products because of their tonic effects and high safety. Their key bioactive components include polysaccharides, which are hydrophilic biomolecules that have demonstrated significant potential in the food and pharmaceutical industries because of their multiple health-promoting qualities, such as immunomodulatory, antitumor, antiaging, blood glucose and blood lipid regulation, antiviral, hepatoprotective, and gastrointestinal protective properties. Additionally, polysaccharides are abundant in health products made from the genus Panax, such as energy drinks and herbal teas. However, compared with more extensively studied components, such as ginsenosides and saponins, polysaccharides from the genus Panax (GPPs) have been the subject of relatively limited research. This review provides a comprehensive overview of the extraction and purification technology, structural characteristics, biological activities, applications, and structure-activity relationships of GPPs. Ultimately, this information establishes a theoretical foundation for the further development and application of GPPs in nutrition and medicine.

Lentinus edodes serves as a significant source of both medicine and food, with its key component, lentinan (LNT), recognized as an effective immunomodulator. However, the mechanisms by which it regulates immune and intestinal functions under conditions of immunosuppression remain unclear. This study aims to investigate the components of lentinan and examine its potential effects on countering cyclophosphamide (CP)-induced immunosuppression, intestinal barrier damage, and dysregulation of gut microbiota. In this study, the effects of LNT were evaluated by serological indicators, histopathological changes in ileum, tight-junction-related protein expression, cytokine expression levels, and gut microbiota 16S rRNA gene sequencing. We found that LNT was effective in mitigating the abnormalities in body weight, immune organ index, and serum levels of IL-6, IL-2, IFN-γ, and IgG in mice induced by CP (p < 0.05). Furthermore, LNT demonstrated the ability to alleviate intestinal barrier damage induced by CP by increasing the mRNA levels of TNF-α, IL-1β, IFN-γ, Occludin, and ZO-1 (p < 0.05). Additionally, 16S rRNA gene sequencing revealed that LNT also normalized the disrupted abundance of Firmicutes, Proteobacteria, and Bacteroidets caused by CP. This restoration brought the gut microbiota back to normal levels and increased the abundance of certain tumor-inhibiting bacteria, such as Alistipes. Overall, lentinan demonstrated the ability to reverse the immunosuppressive effects induced by cyclophosphamide and modulate gut microbiota to restore a healthy microbial balance.

Qiwei Baizhu Powder (QWBZP) has been proven effective in treating antibiotic-associated diarrhea (AAD), and the mechanism is associated with regulating the gut microbiota. However, the role of the bioactive compounds of QWBZP in regulating the gut microbiota is still unclear. In this study, 24 mice were divided into a normal control group (N), a model group (R), a QWBZP decoction group (TW), and a QWBZP-TG group (TG). AAD mouse models were established by mixed antibiotic administration. After modeling, mice in the TW group and TG group were treated with QWBZP decoction and QWBZP-TG, respectively. Mice in the N group and R group were gavaged with sterile water. 16S rRNA gene sequencing was used to investigate the changes of mucosa-associated microbiota (MAM) in the small intestine of mice. Moreover, the levels of diamine oxidase (DAO), D-Lactate, secretory immunoglobulin A (sIgA), interleukin 6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA) kits. The results showed that QWBZP-TG significantly altered the diversity, structure, and abundance of MAM in the AAD mice. QWBZP-TG exerted a stronger suppression effect on Escherichia and Clostridium compared with QWBZP decoction. Meanwhile, QWBZP-TG downregulated the abundance of Lactobacillus, which elicited an opposite effect to QWBZP decoction. Prevotella was the signature bacteria that responded to the QWBZP-TG intervention. Furthermore, both QWBZP decoction and QWBZP-TG decreased the levels of DAO, D-Lactate, sIgA, IL-6, and TNF-α in the AAD mice. The role of glycosides is to help QWBZP ameliorate diarrhea symptoms by inhibiting the proliferation of diarrhea-associated bacteria, reducing inflammation and regulating immunity.

Immunosuppression undermines intestinal barrier integrity. Cow placenta extract (CPE) primarily consists of active peptides with immunomodulatory and antioxidant effects. This study aimed to examine the preventive effect of CPE against intestinal damage induced by cyclophosphamide (Cy) in immunosuppressed mice. Thirty-six mice were randomly allocated into three groups: control group (C), model group (M), and treatment group (CPE). The mice in the CPE group were provided with 1500 mg/kg/day of CPE via gavage. In the last 3 days, mice in the groups M and CPE received intraperitoneal injections of 80 mg/kg/day of Cy. The results showed that CPE improved intestinal barrier function by decreasing serum d-Lactate (D-LA) levels and diamine oxidase (DAO) activity, while elevating the relative expression of Occludin, zonula occludens-1 (ZO-1), and mucin-2 (MUC-2) mRNA. Additionally, CPE improved the immune organ index and elevated the levels of secretory immunoglobulin A (sIgA), superoxide dismutase (SOD), interleukin-1beta (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the intestine, thereby enhancing intestinal mucosal immune function. Furthermore, CPE improved the diversity of intestinal microbiota and increased the abundance of Candidatus_Saccharimonas, Psychrobacter, and Enterorhabdus, which promoted the proper functioning of the intestines. These findings suggest that CPE effectively ameliorates Cy-induced intestinal damage by enhancing the intestinal barrier, improving immune function, and restoring intestinal microbiota.

The diet in early life is essential for the growth and intestinal health later in life. However, beneficial effects of a diet enriched in branched short-chain fatty acids (BSCFAs) for infants are ambiguous. This study aimed to develop a novel fermented protein food, enriched with BSCFAs and assess the effects of dry and wet ferment products on young pig development, nutrient absorption, intestinal barrier function, and gut microbiota and metabolites. A total of 18 young pigs were randomly assigned to three groups. The dry corn gluten-wheat bran mixture (DFCGW) and wet corn gluten-wheat bran mixture (WFCGW) were utilized as replacements for 10% soybean meal in the basal diet. Our results exhibited that the WFCGW diet significantly increased the growth performance of young pigs, enhanced the expression of tight junction proteins, and regulated associated cytokines expression in the colonic mucosa. Simultaneously, the WFCGW diet led to elevated levels of colonic isobutyric and isovaleric acid, as well as the activation of GPR41 and GPR109A. Furthermore, more potential probiotics including Lactobacillus, Megasphaera, and Lachnospiraceae_ND3007_group were enriched in the WFCGW group and positively associated with the beneficial metabolites such as 5-hydroxyindole-3-acetic acid. Differential metabolite KEGG pathway analysis suggested that WFCGW might exert gut health benefits by modulating tryptophan metabolism. In addition, the WFCGW diet significantly increased ghrelin concentrations in serum and hypothalamus and promoted the appetite of young pigs by activating hypothalamic NPY/AGRP neurons. This study extends the knowledge of BSCFAs and provides a reference for the fermented food application in the infant diet.

Our previous study has demonstrated that sulfated Chinese yam polysaccharide (SCYP) can improve immunomodulatory activity in Raw 264.7 cells. However, its anti-inflammatory is little known. In this study, the anti-inflammatory effects of SCYP were systematically investigated via the Lipopolysaccharides (LPS)-induced Raw264.7 cell model, Caco-2/Raw264.7 co-culture system, and acute inflammation mice model. The results suggested SCYP promoted the cell proliferation and have no toxicity in Raw264.7 and Caco-2 cells at the concentration of 200 µg/mL. Moreover, when treated with SCYP, the production of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) reduced significantly in Raw264.7 via the MAPK/NF-κB pathway. In the Caco-2/Raw264.7 co-cultured system, SCYP could regulate inflammation reaction by improving intestinal barrier, which might prevent systemic inflammation. Further, systemic inflammation was alleviated by SCYP in LPS-induced acute inflammation mice through MAPK/NF-κB pathway. PRACTICAL APPLICATION: These results supported that SCYP may be used as an anti-inflammation agent in the functional food field.

Intestinal microbiota and its metabolites are involved in many physiological processes of the human body and play a vital role in maintaining human health. The occurrence of kidney disease can cause intestinal microbiota imbalance, resulting in diarrhea. The change of intestinal microbiota and its metabolites content can aggravate renal function injury, which has a bidirectional regulating effect. The theory of renal-intestinal axis further clarified that the impaired renal function is related to the imbalance of intestinal microorganisms, and the impaired intestinal barrier is related to the accumulation of toxin products. Because of its unique therapeutic advantages, Traditional Chinese Medicine can treat diarrhea by enhancing the growth of beneficial bacteria, inhibiting pathogenic bacteria and immune regulation, and slow down the continuous deterioration of kidney disease. This paper focuses on the relationship between intestinal microbiota and its metabolites and diarrhea, the influence of Traditional Chinese Medicine on intestinal microbiota in the treatment of diarrhea, and the role of intestinal microbiota and its metabolites in the renal-intestinal axis. It provides a theoretical basis for Traditional Chinese Medicine to regulate intestinal microbiota and its metabolites based on the renal-intestinal axis theory to treat nephrology-induced diarrhea, and also provides a new idea and method for Traitional Chinese Medicine to treat nephrology-induced diarrhea.

Polysaccharides are one of the most important components of traditional Chinese medicine (TCM) and have been extensively studied for their immunomodulatory properties. The functions and effects of TCM polysaccharides are closely related to the gut microbiota, making the study of their interaction a hot topic in the field of TCM metabolism. This review follows two main inquiries: first, how the gut microbiota breaks down TCM polysaccharides to produce bioactive metabolites; and second, how TCM polysaccharides reshape the gut microbiota as a carbon source. Understanding the interaction mechanism involves a challenging equation of the structural association of TCM polysaccharides with the metabolic activities of the microbiota. This review has meticulously searched, partially organized literature spanning the past decade, that delves into the interaction mechanism between TCM polysaccharides and gut microbiota. It also gives an overview of the complex factors of the elusive "polysaccharides-bond-bacteria-enzyme" equation: the complexity of polysaccharide structures, the diversity of glycosidic bond types, the communal nature of metabolizing microbiota, the enzymes involved in functional degradation by microbiota, and the hierarchical roles of polysaccharide utilization locus and gram-positive PULs. Finally, this review aims to facilitate discussion among peers in the field of TCM microbiota and offers prospects for research in related fields, paving the way for pharmacological studies on TCM polysaccharides and gut microbiota therapeutics, and providing a reference point for further clinical research.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) has limited its clinical application. It is crucial to discover more effective substances to treat DIC. In this study, a zebrafish model is used to evaluate the inhibition of DIC in the lipids in American ginseng (AGL) compared with the lipids in soybeans (SOL) and in egg yolks (YOL). A lipidomics approach based on Q Exactive LC-MS/MS is employed to monitor, identify, and analyze the lipid composition of three lipid samples. The H9c2 cell was used to investigate the key lipid in AGL for its effect mechanism in alleviating DIC. The results showed that AGL alleviated DIC on zebrafish by increasing the stroke volume, heart rate, and fractional shortening compared to SOL and YOL. A total of 216 differential lipids were identified among the three types of lipids using lipidomics. Besides, a fatty acid with 18 carbons and four double bonds, FA (18:4) was the dominant proportion in AGL and possessed the highest variable importance of projection (VIP) value. FA (18:4) also showed significant bioactivity to alleviate DIC in zebrafish. Furthermore, FA (18:4) reduced the ferric ions and reactive oxygen species (ROS) accumulation, increased GPX4 expression, and relieved mitochondrial damage to inhibit Dox-induced ferroptosis in H9c2 cells. Therefore, the composition characteristic and anti-DIC effect of AGL were revealed; FA (18,4) was identified for the first time to be a novel active component of AGL against DIC by inhibiting ferroptosis. These results provide a new understanding of AG-derived bioactive lipids and their potential benefits for heart health.

Ulcerative colitis (UC) results in inflammation and ulceration of the colon and the rectum's inner lining. The application of herbal therapy in UC is increasing worldwide. As natural macromolecular compounds, polysaccharides have a significant role in the treatment of UC due to advantages of better biodegradation, good biocompatibility, immunomodulatory activity, and low reactogenicity. Therefore, polysaccharide drug formulation is becoming a potential candidate for UC treatment. In this review, we summarize the etiology and pathogenesis of UC and the therapeutic effects of polysaccharides on UC, such as regulating the expression of cytokines and tight junction proteins and modulating the balance of immune cells and intestinal microbiota. Polysaccharides can also serve as drug delivery carriers to enhance drug targeting and reduce side effects. This review provides a theoretical basis for applying natural plant polysaccharides in the prevention and treatment of UC.

American ginseng (Panax quinquefolium L.) is used as tonic plant and high-grade nourishment. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was established for identifying the chemical constituent in three morphological regions of American ginseng, including main root (MR), rhizome (RH) and lateral root (LR). The 63 saponins was identified in different morphological regions of 10 American ginseng samples. The chemical maker compounds in corresponding morphological region, while the major compounds of MR (malonyl-ginsenoside Rb1, ginsenoside Rd, Rs2 and pseudo-RC1), LR (stipuleanoside R2, ginsenoside Re and malonyl-ginsenoside Rc), and RH (malonyl-ginsenoside Rd, Rb3, and chikusetsu saponin II) were discovered. Correlation analysis showed that 11 compounds were positively correlated with the antioxidant activity of American ginseng.

The online version contains supplementary material available at 10.1007/s10068-023-01453-4.

Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway.

The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry.

Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability.

Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.

To explore the mechanism of YGS anti-gastric cancer and immune regulation.

Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.

Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.

YGS has the effect of anti-gastric cancer and immune regulation.

Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome.

The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae_NK4A136_group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis.

The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.

Intestinal inflammatory imbalance and immune dysfunction may lead to a spectrum of intestinal diseases, such as inflammatory bowel disease (IBD) and gastrointestinal tumors. As the king of herbs, ginseng has exerted a wide range of pharmacological effects in various diseases. Especially, it has been shown that ginseng and ginsenosides have strong immunomodulatory and anti-inflammatory abilities in intestinal system. In this review, we summarized how ginseng and various extracts influence intestinal inflammation and immune function, including regulating the immune balance, modulating the expression of inflammatory mediators and cytokines, promoting intestinal mucosal wound healing, preventing colitis-associated colorectal cancer, recovering gut microbiota and metabolism imbalance, alleviating antibiotic-induced diarrhea, and relieving the symptoms of irritable bowel syndrome. In addition, the specific experimental methods and key control mechanisms are also briefly described.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1β, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.

American ginseng (Panax quinquefolius) has gained recognition as a medicinal and functional food homologous product with several pharmaceutical, nutritional, and industrial applications. However, the key regulators involved in ginsenoside biosynthesis, the spatiotemporal distribution characteristics of ginsenosides, and factors influencing ginsenosides are largely unknown, which make it challenging to enhance the quality and chemical extraction processes of the cultivated American ginseng. This review presents an overview of the pharmacological effects, biosynthesis and spatiotemporal distribution of ginsenosides, with emphasis on the impacts of biotic and abiotic factors on ginsenosides in American ginseng. Modern pharmacological studies have demonstrated that American ginseng has neuroprotective, cardioprotective, antitumor, antidiabetic, and anti-obesity effects. Additionally, most genes involved in the upregulation of ginsenoside biosynthesis have been identified, while downstream regulators (OSCs, CYP450, and UGTs) require further investigation. Futhermore, limited knowledge exists regarding the molecular mechanisms of the impact of biotic and abiotic factors on ginsenosides. Notably, the nonmedicinal parts of American ginseng, particularly its flowers, fibrous roots, and leaves, exhibit higher ginsenoside content than its main roots and account for a considerable amount of weight in the whole plant, representing promising resources for ginsenosides. Herein, the prospects of molecular breeding and metabolic engineering based on multi-omics to improve the unstable quality of cultivated American ginseng and the shortage of ginsenosides are proposed. This review highlights the gaps in the current research on American ginseng and proposes solutions to address these limitations, providing a guide for future investigations into American ginseng ginsenosides.

As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.

The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.

Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.