Enterococcus faecalis-infected macrophages produce 4-hydroxynonenal (4-HNE) that mediates microbiota-induced bystander effect (MIBE) leading to colorectal cancer (CRC). Glutathione S-transferase alpha 4 (Gsta4), a specific detoxifying enzyme for 4-HNE, is overexpressed in human CRC and E. faecalis-induced murine CRC. However, the roles of Gsta4 in E. faecalis-induced colitis and CRC remain unclear. Herein, we demonstrate that Gsta4 is essential for MIBE by protecting macrophages from E. faecalis-induced ferroptosis. E. faecalis OG1RFSS was used to induce colitis in Gsta4-/- and Il10-/-/Gsta4-/- mice by orogastric gavage. Ferroptosis was assessed in Gsta4-deficient murine macrophages. We found that, unlike Il10-/- mice, Gsta4-/- and Il10-/-/Gsta4-/- mice colonized with E. faecalis failed to develop colitis or CRC. Immunofluorescent staining showed a reduction of macrophages in the lamina propria of E. faecalis-colonized Il10-/-/Gsta4-/- mice, as well as decreased Gpx4 expression, indicating the occurrence of ferroptosis. Ferroptosis was further confirmed in Gsta4-deficient murine macrophages infected with E. faecalis. Moreover, Gsta4 inactivation induced the upregulation of Hmox1 and phosphorylated c-Jun while blocked Nos2 expression, leading to the accumulation of intracellular ferrous iron, lipid peroxidation and, eventually, ferroptosis. Finally, Mapk8, as a ferroptosis driver, was remarkably elevated in E. faecalis-infected Gsta4-deficient macrophages. These results suggest that Gsta4 inactivation blocks MIBE by eliminating macrophages, thereby attenuates E. faecalis-induced colitis and CRC.

Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

The focus of this study is to explore the impact of gut microbiota in different states on the blood components of couplet medications (dried toad skin and radix clematidis) and to identify drug metabolites associated with the gut microbiota. By constructing a pseudo-sterile rat model and combining non-targeted metabolomics with plasma pharmacology, we found that the plasma metabolites of couplet medications underwent significant changes in different gut microbiome environments. The GABA and PGE1 levels in the model group and the model+TCM (traditional chinese medicine) group were both significantly lower than those in the normal+TCM group. When the gut microbiota is imbalanced, drug interventions cannot significantly increase the levels of GABA and PGE1. It further confirmed the correlation between the levels of GABA and PGE1 and the gut microbiota. Based on the results of non-targeted metabolomics, we applied network pharmacology and molecular docking to explore the core targets for colorectal cancer treatment based on gut microbiota. In the end, we identified TNF and PPARG as the two core targets. These research findings provide a possibility for clarifying the molecular mechanisms of couplet medications in the treatment of colorectal cancer. It also laid the foundation for further clarifying the molecular mechanisms of Chanling Paste in the treatment of colorectal cancer.

The human gut microbiome's role in colorectal cancer (CRC) pathogenesis has gained increasing recognition. This study aimed to delineate the microbiome characteristics that distinguish CRC patients from healthy individuals, while also evaluating the influence of aging, through a comprehensive metagenomic approach. The study analyzed a cohort of 80 CRC patients and 80 matched healthy controls, dividing participants into a normal and a CRC group, further categorized by age into young, middle-aged, and old-aged subgroups. Extensive metagenomic sequencing of fecal samples allowed for the exploration of both the structural and functional profiles of the microbiome, with findings validated in an independent cohort to ensure robustness. Our results highlight notable differences in microbiome composition between CRC patients and healthy individuals, which exhibit age-dependent variations. Specifically, a higher prevalence of pathogenic bacteria, such as Bacteroides vulgatus, known to drive inflammation and carcinogenesis, was observed in CRC patients, alongside a reduction in beneficial microbes, including Lactobacillus. Functionally, the CRC-associated microbiome showed an increase in pathways related to DNA repair, cell cycle regulation, and metabolic activities, such as the Citrate cycle and Galactose metabolism, underscoring distinct microbial alterations in CRC patients that could influence disease onset and progression. These insights lay a foundation for future research into microbiome-based diagnostics and treatments for CRC.

This study underscores the critical role of the gut microbiome in colorectal cancer (CRC) pathogenesis, particularly in the context of aging. By identifying age-specific microbial biomarkers and functional pathways associated with CRC, our findings provide novel insights into how microbiome composition and metabolic activities influence disease progression. These discoveries pave the way for developing personalized microbiome-based diagnostic tools and therapeutic strategies, potentially improving CRC prevention and treatment outcomes across different age groups. Understanding these microbial dynamics could also inform interventions targeting gut microbiota to mitigate CRC risk and progression.

To better understand the impact of microbial interactions on the clonal evolution of colorectal cancer (CRC), we conducted high-resolution profiling of the gut microbiome of 101 treatment-naïve primary CRC patients using nanopore sequencing. We performed an integrated analysis of microbiome and tumor exome data to identify symbiotic microbes that interactively influence the mutational processes and the subsequent clonality of CRC. Our results suggested that Dialister pneumosintes and Fusobacterium animalis were both associated with somatic EPPK1 mutations and promote SBS6 (mismatch repair deficiency, dMMR) activity. Notably, we showed that the symbiotic architecture of Dialister pneumosintes and Fusobacterium animalis undergoes significant changes with the mutational status of EPPK1. In addition, we identified specific metabolic pathways involving key metabolites that potentially mediate microbial interactions in CRC. These findings provide new insights into the interplay between the gut microbiome and the mutation landscape of colorectal cancer, thereby informing the clonal evolution of CRC and new strategies for precision medicine.

Collecting fecal samples using dry preservatives is an attractive option in large epidemiological studies as they are easy to use, cheap and independent of cold chain logistics. Here, we test four DNA extraction methods with the aim of identifying an efficient procedure to extract high-quality DNA from fecal material of canine, sheep, equine, bovine, and pig collected on dry blood spot cards, with the goal of generating good quality shotgun metagenomics datasets. Further, the suitability of Illumina shotgun metagenomic sequencing at 20 million paired-end (PE) read depth per sample was assessed on its ability to successfully characterize the taxonomic and functional aspects of the resulting fecal microbiome.

DNA was extracted from pig feces and mock communities collected on blood spot cards using four DNA extraction methods; two different methods of the QIAsymphony® PowerFecal® Pro DNA Kit, the ZymoBIOMICS™ DNA Miniprep Kit, and the MagNA Pure 96 DNA and Viral NA Small Volume Kit. Possible extraction bias was controlled by amplicon sequencing of mock communities. Fecal samples from canine, sheep, equine, bovine, and pig were thereafter subjected to the best performing DNA extraction method and shotgun metagenomic sequencing to determine sequencing efforts for functional and taxonomic analysis.

The four DNA extraction methods demonstrated similar community composition in the sequenced bacterial mock community. The QIAsymphony® PowerFecal® Pro DNA Kit was identified as the DNA extraction method of choice, and the resulting DNA was subjected to shotgun metagenomic sequencing with 20million PE reads. We found that higher number of reads increased the richness of observed genera between 100,000 and 5 million reads, after which higher sequencing effort did not increase the richness of the metagenomes. As for functional analysis, the number of low abundance functions in the metagenomes of the animals' feces increased with sequencing depth above 20 million PE reads.

Our experiments identified several methods suitable for extracting DNA from feces collected on blood spot cards. The QIAGEN's Blood and Tissue kit on the QiaSymphony platform fulfilled the criteria of high yield, quality, and unbiased DNA, while maintaining high throughput for shotgun metagenomic sequencing. A sequencing depth of 20 million PE reads proved adequate for taxonomic estimations and identifying common functional pathways. Detecting rarer traits, however, requires more sequencing effort.

Colorectal cancer (CRC), as one of the most common cancers globally, poses a significant challenge to public health due to its high incidence and mortality rates. This underscores the need for continuous exploration of new therapeutic targets and effective drugs. Sophocarpine (SC), a natural compound derived from traditional Chinese medicine, holds considerable therapeutic potential in the treatment of CRC, however, the relevant mechanisms remains unclear.

This study aims to explore the anti-tumor effects of SC against CRC by modulating gut microbiota, and uncover potential mechanisms linking SC's therapeutic effects to gut microbiota regulation by analyzing the impact of SC on microbiota composition and CRC progression.

This study explores the impact of SC on the gut microbiota in CRC by constructing subcutaneous xenograft tumors of CRC and integrating 16S rRNA sequencing and RNA transcriptomic sequencing. The fecal microbiota transplantation (FMT) mouse model was used to validate the biological function of SC in correcting gut microbiota dysbiosis to treat CRC. Subsequently, we conducted in vitro studies on the molecular mechanisms by which SC regulates the gut microbiota as an effective hallmark of CRC treatment, using lipopolysaccharide (LPS) to simulate an inflammatory gut microbiota environment and P38 MAPK knockdown cell line.

SC significantly inhibited CRC cell proliferation with IC50 values of 2.547±0.256 μM for HCT116 and 2.851±0.332 μM for LoVo cells. In vivo experiments demonstrated that SC effectively suppressed tumor growth in xenograft models. 16S rRNA sequencing revealed that SC modulated gut microbiota composition, particularly affecting Bacteroides and Alistipes populations. SC significantly reduced the levels of inflammatory factors and inhibited the MAPK signaling pathway, as evidenced by decreased p-JNK, p-p38 MAPK, and p-NF-κB p65 expression.

Current clinical practice still lacks effective therapeutic agents targeting CRC through gut microbiota modulation. This study presents the first evidence that SC, a natural compound, exhibits dual-action therapeutic efficacy against CRC progression by simultaneously modulating gut microbial composition and suppressing MAPK pathway-mediated inflammatory responses. These findings highlight SC's novel therapeutic potential as a promising microbiota-regulating candidate for CRC intervention, offering an innovative approach that bridges microbial ecology with cancer signaling pathways.

Colorectal cancer (CRC), especially low rectal cancer, often requires surgical resection of the anus, which severely affects the quality of life of patients. This study aims to develop a novel treatment method that can effectively control tumor growth while preserving anal function. We design a radioactive hydrogel (177Lu-RH) based on the cross-linking of metal ions and sodium alginate, which can be directly injected into the tumor to achieve local radiotherapy. In mouse experiments, we observe significant differences in the therapeutic efficacy of 177Lu-RH among treated mice. Through 16S rDNA microbial diversity and targeted metabolomics studies, it has been revealed that the intestinal microbiota, particularly the Rikenella bacteria, and their metabolite propionate, are positively correlated with a favorable treatment response. We subsequently select the genus Rikenella, which exhibit a significantly higher abundance in the near-complete response (nCR) compared to the partial response (PR) group, for further mechanistic investigation. We discover that propionate, a metabolite produced by Rikenella, plays a crucial role in promoting tumor cell apoptosis and may augment the efficacy of tumor immunotherapy. Therefore, we improve the radioactive hydrogel by adding sodium propionate (SP) to form 177Lu-RH@SP. In vivo experiments show that 177Lu-RH@SP combined with anti-programmed death ligand 1 (αPD-L1) not only inhibits tumor growth but also promotes DC maturation and reverses T cell exhaustion, thereby enhancing the efficacy of tumor immunotherapy. Our work provides a new approach for the treatment of low rectal tumors, with the potential to improve the prognosis and quality of life for patients.

Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.

Objectives: The dietary inflammatory index (DII), a validated tool for assessing the inflammatory potential of diet, has been widely identified as a significant risk factor for colorectal cancer (CRC). However, its role as a prognostic factor for CRC remains unexplored. This study examined the impact of preoperative dietary inflammation on clinical and oncologic outcomes following CRC surgery. Methods: The study population consisted of 126 patients who had surgical procedures for CRC and completed a food frequency questionnaire (FFQ) preoperatively between January 2018 and June 2020. Results: An optimal DII cut-off value of 0.90182 was used to categorize patients into the high-DII (n = 28) and low-DII (n = 98) groups. The high-DII group exhibited an older age (71.5 vs. 67.0, p = 0.020) and a significantly higher complication risk within 30 days postoperatively than the low-DII group (57.1% vs. 35.7%, p = 0.042). Other perioperative clinical outcomes did not demonstrate any significant differences between the two groups. The 5-year overall survival (OS) rates were 90.4% and 41.3% in the low-DII and high-DII groups, respectively, in univariate survival analysis (p = 0.044). However, no statistical difference was observed in the disease-free survival (DFS) rate. In the multivariate survival analysis, low-DII (hazard ratio [HR]: 0.118; 95% confidence interval [CI]: 0.023-0.613, p = 0.011) and M1 stage (HR: 10.910; 95% CI: 1.491-79.847, p = 0.019) were identified as independent prognostic factors for OS, while perineural invasion (HR: 3.495; 95% CI: 1.059-11.533, p = 0.040) served as an independent prognostic factor for DFS. Conclusions: A high preoperative DII score, indicative of an inflammatory dietary pattern, was correlated with increased postoperative complications and functioned as an independent prognostic indicator for OS.

Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these malignancies. RCRC and LCRC differ not only in clinical presentation and outcomes but also in their underlying molecular and genetic profiles. This article offers a detailed literature review focusing on the distinctions between RCRC and LCRC. We explore key differences across embryology, anatomy, pathology, omics, and the tumor microenvironment (TME), providing insights into how these factors contribute to prognosis and therapeutic responses. Furthermore, we examine the therapeutic implications of these differences, considering whether the conventional classification of CRC into right- and left-sided forms should be refined. Recent molecular findings suggest that this binary classification may overlook critical biological complexities. Therefore, we propose that future approaches should integrate molecular insights to better guide personalized treatments, especially anti-EGFR therapies, and improve patient outcomes.

Chimeric antigen receptor-T (CAR-T) cell therapy is a cellular immunotherapy that has emerged in recent years, and increasing studies showed that therapeutic resistance to CAR-T cell therapy presents in colorectal cancer patients. Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is known to preserve a high concentration in the colon. Whether LPS is a contributing factor to the development of resistance in colorectal cancer cells against CAR-T cell therapy remains unclear. For in vivo experiments, colorectal cancer cells COLO205 were pretreated with LPS for 24 h and then were injected into nude mice through the tail vein, followed by CAR-T cells transplantation one day later. Later, the number of tumors in the lung tissues of the mice was observed. The in vitro experiments were performed on COLO205 cells, which were treated with LPS for 24 h. The effect of LPS on the stemness of COLO205 and SW620 cells was observed by using the colony formation assay and spheroidization experiments. The effect of LPS on the expression of stemness-related genes, including CD44, SOX2, and NANOG, was observed by qRT-PCR assay, Western blotting assay, and immunofluorescence staining. Inhibitors of TGF-β and the MYD88 inhibitor were used to study the mechanisms by which LPS induces the stemness enhancement and resistance to CAR-T cell therapy of COLO205 cells. The correlation between MYD88 and TGFB1, as well as the correlation between TGFB1 and stemness-related genes was analyzed using the TCGA database. Both the in vivo assay of nude mice and the in vitro assay showed that LPS pretreatment could induce resistance to CAR-T cell therapy of colorectal cancer cells. LPS could enhance COLO205 and SW620 cells stemness presented by upregulation of CD44, SOX2, and NANOG. The reverse interfering assay using the TGF-β inhibitor indicated that the autosecretion of TGF-β induced by LPS played a critical role in the stemness enhancement of colorectal cancer cells. The TCGA database analysis revealed a strong positive correlation between MYD88 and TGFB1. Additionally, TGFB1 has been found to upregulate the expression of genes associated with stemness. Further mechanism studies showed that the TLR4/MYD88 pathway medicates LPS-induced TGF-β expression. Our results suggested that LPS-induced resistance to CAR-T cell therapy of colorectal cancer cells through stemness enhancement. TLR4/MYD88 signal pathway-dependent TGF-β expression was involved in stemness enhancement and CAR-T cell therapy resistance. In conclusion, our findings help us to understand the underlying mechanisms of CAR-T cell therapy resistance and indicate that inhibitors of TGF-β and MYD88 are promising targeting candidates to promote a therapeutic effect of CAR-T cell therapy in colorectal cancer in the clinic.

Diet, microbiome, inflammation and host genetics have been linked to colorectal cancer development; however, it is not clear whether and how these factors interact to promote carcinogenesis. Here we used Il10-/- mice colonized with bacteria previously associated with colorectal cancer: enterotoxigenic Bacteroides fragilis, Helicobacter hepaticus or colibactin-producing (polyketide synthase-positive (pks+)) Escherichia coli and fed either a low-carbohydrate (LC) diet deficient in soluble fibre, a high-fat and high-sugar diet, or a normal chow diet. Colonic polyposis was increased in mice colonized with pks+ E. coli and fed the LC diet. Mechanistically, mucosal inflammation was increased in the LC-diet-fed mice, leading to diminished colonic PPAR-γ signalling and increased luminal nitrate levels. This promoted both pks+ E. coli growth and colibactin-induced DNA damage. PPAR-γ agonists or supplementation with dietary soluble fibre in the form of inulin reverted inflammatory and polyposis phenotypes. The pks+ E. coli also induced more polyps in mismatch-repair-deficient mice by inducing a senescence-associated secretory phenotype. Moreover, oncogenic effects were further potentiated by inflammatory triggers in the mismatch-repair-deficient model. These data reveal that diet and host genetics influence the oncogenic potential of a common bacterium.

To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS).

A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high-throughput sequencing of the 16S rRNA microbial gene.

Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-β1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased.

BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

Cancer is a global health challenge, and its development is closely linked to iron metabolism. Cancer cells have an increased demand for this element, which promotes their proliferation, invasion, and metastasis. Excess iron catalyzes the formation of reactive oxygen species (ROS), which can both induce ferroptosis and initiate oncogenic signaling pathways. The deregulation of iron metabolism in cancer patients leads to anemia or toxic iron overload and also affects the gut microbiota. Lactoferrin (LF), a glycoprotein with strong iron chelating properties, can regulate its availability to cancer cells, thereby limiting their growth and progression. By chelating free Fe ions, LF reduces oxidative stress and inhibits the mechanisms that promote carcinogenesis. Additionally, it exhibits immunomodulatory and anti-inflammatory effects and may enhance the body's anti-tumor response. This review analyses the mechanisms of action of lactoferrin in the context of cancer, with a particular focus on its chelating, antioxidant, and immunomodulatory properties. The multidirectional effects of LF make it a promising component of preventive and therapeutic strategies, requiring further clinical studies.

Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.

Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.

Colorectal liver metastasis (CRLM) represents a major therapeutic challenge in colorectal cancer (CRC), with complex interactions between the gut microbiota and the liver tumor microenvironment (TME) playing a crucial role in disease progression via the gut-liver axis. The gut barrier serves as a gatekeeper, regulating microbial translocation, which influences liver colonization and metastasis. Through the gut-liver axis, the microbiota actively shapes the TME, where specific microbial species and their metabolites exert dual roles in immune modulation. The immunologically "cold" nature of the liver, combined with the influence of the gut microbiota on liver immunity, complicates effective immunotherapy. However, microbiota-targeted interventions present promising strategies to enhance immunotherapy outcomes by modulating the gut-liver axis. Overall, this review highlights the emerging evidence on the role of the gut microbiota in CRLM and provides insights into the molecular mechanisms driving the dynamic interactions within the gut-liver axis.

Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.

The developmental origins of health and disease (DOHaD) concept suggests that adverse conditions during gestation can influence the development and function of multiple organs, including the gastrointestinal tract. Maternal protein restriction (MPR) exposure has been associated with negative effects on reproduction, the endocrine system, and liver metabolic health. However, limited research has explored the impact of MPR on the offspring's intestinal morphophysiology. This study investigated the effects of gestational and lactational MPR on the duodenum and colon of young male offspring rats at postnatal (PND)21. We hypothesize that MPR affects intestinal morphophysiology and development early in life. Our findings revealed tachygastria in offspring exposed to MPR. The ultrastructural analysis uncovered a reduction in goblet cell numbers and changes in collagen deposition in the duodenum and colon. We also identified imbalances in inflammatory markers (IL-6 and TGF-β1) and antioxidant enzymes (CAT and SOD). These results demonstrate that MPR significantly affects gastrointestinal morphophysiology early in life by disrupting gastric motility and altering duodenal and colonic histoarchitecture, antioxidant defense, and inflammatory pathways. Such alterations may predispose the descendants to long-term gastrointestinal disorders, underscoring the importance of further research on the developmental origins of intestinal health and disease.

The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.

The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.

Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.

The dysregulation of intestinal microbiota has been implicated in the pathogenesis of colorectal cancer (CRC). However, the utilization of intestinal microbiota for identify the lesions in different procedures in CRC screening populations remains limited.

A total of 529 high-risk individuals who underwent CRC screening were included, comprising 13 advanced adenomas (Aade), 5 CRC, 59 non-advanced adenomas (Nade), 129 colon polyps (Pol), 99 cases of colorectal inflammatory disease (Inf), and 224 normal controls (Nor). 16S rRNA gene sequencing was used to profile the intestinal microbiota communities. The Gut Microbiota Health Index (GMHI) and average variation degree (AVD) were employed to assess the health status of the different groups.

Our findings revealed that the Nor group exhibited significantly higher GMHIs and the lowest AVD compared to the four Lesion groups. The model incorporating 13 bacterial genera demonstrated optimal efficacy in distinguishing CRC and Aade from Nor, with an area under the curve (AUC) of 0.81 and a 95% confidence interval (CI) of 0.72 to 0.89. Specifically, the 55 bacterial genera combination model exhibited superior performance in differentiating CRC from Nor (AUC 0.98; 95% CI, 0.96-1), the 25 bacterial genera combination showed superior performance in distinguishing Aade from Nor (AUC 0.95). Additionally, the 27 bacterial genera combination demonstrated superior efficacy in differentiating Nade from Nor (AUC 0.82). The 13 bacterial genera combination exhibited optimal performance in distinguishing Inf from Nor (AUC 0.71).

Our study has identified specific microbial biomarkers that can differentiate between colorectal lesions and healthy individuals. The intestinal microbiota markers identified may serve as valuable tools in community-based CRC screening programs.

Colorectal cancer (CRC) is a significant threat to human health. The dynamic equilibrium between probiotics and pathogenic bacteria within the gut microbiota is crucial in mitigating the risk of CRC. An overgrowth of harmful microorganisms in the gastrointestinal tract can result in an excessive accumulation of bacterial toxins and carcinogenic metabolites, thereby disrupting the delicate balance of the microbiota. This disruption may lead to alterations in microbial composition, impairment of mucosal barrier function, potential promotion of abnormal cell proliferation, and ultimately contribute to the progression of CRC. Recently, research has indicated that intestinal presence of Fusobacterium nucleatum (Fn) significantly influences the onset, progression, and metastasis of CRC. Consequently, disrupting the interaction between CRC cells and Fn presents a promising strategy against CRC. Nanomaterials have been extensively utilized in cancer therapy and bacterial infection control, demonstrating substantial potential in treating bacteria-associated tumors. This review begins by elucidating the mechanisms of gut microbiota and the occurrence and progression of CRC, with a particular emphasis on clarifying the intricate relationship between Fn and CRC. Subsequently, we highlight strategies that utilize nanomaterials to disrupt the association between Fn and CRC. Overall, this review offers valuable insight and guidance for leveraging nanomaterials in CRC therapy.

An increasing number of studies have revealed that gut microbiota influences the development and progression of Colorectal cancer (CRC). However, whether a causal relationship exists between the two remains unclear, and the role of immune cells in this context is not well understood.

To elucidate the causal relationship between gut microbiota and CRC and to explore the potential mediating role of circulating immune cells.

To analyze the causal relationship between gut microbiota and CRC, we employed a univariable Mendelian randomization (UVMR) approach. Subsequently, a two-step multivariable Mendelian randomization (MVMR) to assess the potential mediating role of circulating immune cells. Primarily, applied the Inverse-Variance Weighted method to evaluate the causal relationship between exposure and outcome. To ensure the robustness of the results linking gut microbiota and CRC, we validated the findings using Robust Inverse-Variance Weighted, Penalized Inverse-Variance Weighted, and Penalized Robust Inverse-Variance Weighted methods. Additionally, we employed MR-Egger Intercept to mitigate the influence of horizontal pleiotropy. MR-PRESSO was used to detect and correct outliers by excluding anomalous instrumental variables. Finally, we supplemented our analysis with methods such as Bayesian Weighted Mendelian Randomization (BWMR), Maximum-Likelihood, Lasso, Debiased Inverse Variance Weighted, and Contamination Mixture to establish a robust and compelling causal relationship.

After accounting for reverse causality, horizontal pleiotropy, and various methodological corrections, Bifidobacterium kashiwanohense, GCA-900066755 sp900066755, Geminocystis, and Saccharofermentanaceae exhibited strong and robust causal effects on CRC. Specifically, CD40 on monocytes (2.82%) and CD45 on CD33+HLA-DR+CD14- cells (12.87%) mediated the causal relationship between Bifidobacterium kashiwanohense and CRC risk. Furthermore, CD45 on CD33-HLA-DR+ (3.94%) mediated the causal relationship between GCA-900066755 sp900066755 and CRC risk. Additionally, terminally differentiated CD4+T cells (11.55%) mediated the causal relationship between Geminocystis and CRC risk. Lastly, CD40 on monocytes (2.35%), central memory CD4+T cells (5.76%), and CD28 on CD28+CD45RA+CD8+T cells (5.00%) mediated the causal relationship between Saccharofermentanaceae and CRC risk.

Our mediation MR analysis provides genetic evidence suggesting that circulating immune cells may mediate the causal relationship between gut microbiota and CRC. The identified associations and mediation effects offer new insights into potential therapeutic avenues for CRC.

Probiotics have been proposed as a potential strategy for managing ulcerative colitis (UC). However, the underlying mechanisms mediating microbiota-host crosstalk remain largely elusive. Here, we report that Limosilactobacillus reuteri (L. reuteri), as a probiotic, secretes cytoplasmic membrane vesicles (CMVs) that communicate with host cells, alter host physiology, and alleviate dextran sulfate sodium (DSS)-induced colitis. First, L. reuteri-CMVs selectively promoted the proliferation of the beneficial bacterium Akkermansia muciniphila (AKK) by upregulating the expression of glycosidases (beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase) involved in glycan degradation and metabolic pathways and restored the disrupted gut microbiota balance. Second, L. reuteri-CMVs were taken up by intestinal epithelial cells (IECs), elevated the expression of ZO-1, E-cadherin (Cdh1), and Occludin (Ocln), decreased intestinal permeability, and exerted protective effects on epithelial tight junction functionality. RNA sequencing analysis demonstrated that L. reuteri-CMVs repaired intestinal barrier by activating the HIF-1 signaling pathway and upregulating HMOX1 expression. Third, L. reuteri-CMVs increased the population of double positive (DP) CD4+CD8+ T cells in the intestinal epithelial layer, suppressing gut inflammation and maintaining gut mucosal homeostasis. Finally, L. reuteri-CMVs exhibited satisfactory stability and safety in the gastrointestinal tract and specifically targeted the desired sites in colitis mice. Collectively, these findings shed light on how L. reuteri interact with the host in colitis, and provide new insights into potential strategies for alleviating colitis.

Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.

Black ginseng (BG) is of great interest for its anti-cancer property. Its detailed mechanism, however, is still lacking. This study aims to evaluate the effectiveness of ginsenosides 20R-Rg3 and Rg5 enriched BG (Rg3/Rg5-BG), innovatively prepared by low temperature steam-heating process, against colorectal cancer (CRC), and elucidate its potential molecular mechanism. Interestingly, much higher concentrations of rare ginsenosides were detected in this unique BG than those in red ginseng, especially 20R-Rg3 and Rg5, which may contribute to treatment of CRC. As expected, Rg3/Rg5-BG demonstrated a dose-dependent reduction in cancer cell viability, along with the induction of cell apoptosis and cell cycle arrest. Moreover, Rg3/Rg5-BG retarded tumor growth in the model mice, as evidenced by downregulation of anti-apoptotic Bcl-2 protein and phosphatidyl Akt, and upregulation of the apoptotic proteins Bax, caspase-8, and cleaved caspase-3, enhancing apoptosis of tumor cells. Additionally, Rg3/Rg5-BG treatment improved the gut microbiota and intervened with bacteria associated with cancer development, including increasing beneficial probiotics such as Candidatus_Saccharibacteria and Saccharibacteria_genera_incertae_sedis and decreasing pernicious bacteria (Vampirovibrio, Clostridium_XlVb, etc.). Our results manifested for the first time that Rg3/Rg5-BG exerted its anti-cancer effects: through activation of the caspase-3/Bax/Bcl-2 pathway and by altering the gut microbiome composition, thus paving the way for new therapeutic strategies that incorporate natural products in cancer treatment.

Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk, and all-cause mortality in patients with CRC remain unclear.

We analyzed the associations between AL and CRC risk in 304 959 adults and all-cause mortality in 1794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models.

Compared with the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% confidence interval [CI] = 36.16 to 42.32) of CRC events. Meanwhile, a statistically association between the AL and all-cause mortality in patients with CRC was found, with a hazard ratio of 1.71 (95% CI = 1.16 to 2.50) for the fourth quartile compared with the AL score in the first quartile, demonstrating a positive dose-response relationship.

High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.

The treatment of advanced colorectal cancer (CRC) has progressed slowly, with chemotherapy combined with targeted therapy being the first-line treatment for the disease, but the improvement in efficacy is not satisfactory. Compound Kushen injection (CKI) is one of the representative drugs of anti-cancer Chinese herbal injection drugs, which has been widely used in the adjunct treatment of cancer in China. The aim of this trial is to evaluate the efficacy and safety of CKI combined with first-line treatment of advanced CRC.

This is a multicenter, randomized, open-label controlled clinical trial in which 320 patients with advanced CRC will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Both groups will receive at least 4 cycles of first-line therapy (FOLFOX/FOLFIRI/CAPEOX ± cetuximab/bevacizumab) in 14-21 day cycles, and the experimental group will receive additional CKI with a cumulative dose of 200 ml per cycle. Patients who achieve a complete response, partial response, or stable disease after 4-6 months will receive maintenance therapy until disease progression or another endpoint event, such as toxicity or death, occurs.. Follow-up will occur every 3 months until death or loss to follow-up. The primary outcome of this study will be progression-free survival (PFS). Secondary outcomes will be overall survival (OS), 1-year OS rate, 1-year PFS rate, objective response rate,disease control rate, symptoms and quality of life evaluation. Safety outcomes will be incidence of adverse events.

This study will be the first randomized controlled trial to investigate the efficacy and safety of CKI when combined with first-line treatment in the treatment of advanced CRC, with PFS as the primary outcome. It aims to clarify the clinical advantages and therapeutic effect of CKI in the treatment of advanced CRC. To identify the benefit population of CKI in the treatment of patients with advanced CRC, an enrichment design based on biomarkers will be utilized. Metabolomics and gut microbiota analysis will be conducted on biological samples to explore the metabolic and gut microbiota differences associated with the efficacy of CKI, guiding further research into its mechanism of action.

ClinicalTrials.govNCT05894694. Registered on 4 August 2023.

Pangolins, one of the most trafficked mammals, face significant health challenges in captivity, including digestive disorders and immune dysfunctions. These issues are closely linked to alterations in their gut microbiota, which play vital roles in the host metabolism, immunity, and overall health. This study investigated the differences in the gut microbiota composition and function between two pangolin species, Chinese pangolins (Manis pentadactyla) and Malayan pangolins (Manis javanica), under identical captive conditions to better understand their ecological adaptability and health implications. Using metagenomic sequencing, fecal samples from eight adult captive pangolins were analyzed, including four male Malayan pangolins and three male and one female Chinese pangolins. Comparative analyses of the alpha and beta diversities, microbial community structure, and functional profiles were performed. Both species harbored gut microbiota dominated by Firmicutes, Bacteroidetes, and Proteobacteria. However, the Chinese pangolins exhibited higher microbial diversity (Shannon index, p = 0.042; Simpson index, p = 0.037) and lower relative abundance of Proteobacteria compared with the Malayan pangolins. A functional analysis revealed significant differences in the metabolic pathways, where the Chinese pangolins demonstrated a higher potential for fiber degradation, whereas the Malayan pangolins exhibited elevated levels of antibiotic resistance genes and pathogenic taxa, such as Escherichia coli. These findings suggest that captivity duration and environmental stress likely contribute to the observed differences, with the Malayan pangolins experiencing greater dysbiosis due to longer captivity periods. This study provides valuable insights into the role of gut microbiota in pangolin health and offers a foundation for improving conservation strategies and captive care protocols.

Bacteria-mediated antitumor therapy has gained widespread attention for its innate tumor-targeting capability and excellent immune activation properties. Nevertheless, the clinical approval of bacterial therapies remains elusive primarily due to the formidable challenge of balancing safety with enhancing in vivo efficacy. In this study, leveraging the probiotic Escherichia coli Nissle1917 (EcN) emerges as a promising approach for colon cancer therapy, offering a high level of safety attributed to its lack of virulence factors and its tumor-targeting potential owing to its obligate anaerobic nature. Specifically, we delineate the erythrocyte (RBC) membrane-camouflaged EcN, termed as Trojan horse EcN@RBC, which triggers apoptosis in tumor cells by mitigating mitochondrial membrane potential (MMP) and subsequently activating the PINK1/Parkin pathway associated with mitophagy. Concurrently, the decline in MMP induced by mitophagy disrupts the mitochondrial permeability transition pore (MPTP), leading to the release of Cytochrome C and subsequent apoptosis induction. Moreover, synergistic effects were observed through the combination of the autophagy activator rapamycin, bolstering the antitumor efficacy in vivo. These findings offer novel insights into probiotic-mediated antitumor mechanisms and underscore the therapeutic potential of EcN@RBC for colon cancer patients.

Antibiotics are commonly used to treat infectious diseases; however, persistence is often expressed by the pathogenic bacteria and their long-term relative effect on the host have been neglected. The present study investigated the impact of antibiotics in gut microbiota (GM) and metabolism of host. The effect of ampicillin antibiotics on GM of Drosophila melanogaster was analyzed through deep sequencing of 16S rRNA amplicon gene. The dominant phyla consisted of Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, Planctomycetes, Chloroflexi, Euryarchaeota, Acedobacteria, Verrucomicrobia, and Cyanobacteria. It was found that the composition of GM was significantly altered on administration of antibiotics. On antibiotic treatments, there were decline in relative abundance of Proteobacteria and Firmicutes, while there were increase in relative abundance of Chlorophyta and Bacteroidota. High abundance of 14 genera, viz., Wolbachia, Lactobacillus, Bacillus, Pseudomonas, Thiolamprovum, Pseudoalteromonas, Vibrio, Romboutsia, Staphylococcus, Alteromonas, Clostridium, Lysinibacillus, Litoricola, and Cellulophaga were significant (p ≤ 0.05) upon antibiotic treatment. Particularly, the abundance of Acetobacter was significantly (p ≤ 0.05) declined but increased for Wolbachia. Further, a significant (p ≤ 0.05) increase in Wolbachia endosymbiont of D. melanogaster, Wolbachia endosymbiont of Curculio okumai, and Wolbachia pipientis and a decrease in the Acinetobacter sp. were observed. We observed an increase in functional capacity for biosynthesis of certain nucleotides and the enzyme activities. Further, the decrease in antimicrobial peptide production in the treated group and potential effects on the host's defense mechanisms were observed. This study helps shed light on an often-overlooked dimension, namely the persistence of antibiotics' effects on the host.

Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.

This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.

120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.

Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.

The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.

ChiCTR2300076136, retrospectively registered.