An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome.

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.

Short-term arecoline exposure affected the systemic health state of mice, in which gut microbes played an important role.

Arecoline is a critical bioactive component in areca nuts with toxicity and pharmacological activities. However, its effects on body health remain unclear. Here, we investigated the effects of arecoline on physiologic and biochemical parameters in mouse serum, liver, brain, and intestine. The effect of arecoline on gut microbiota was investigated based on shotgun metagenomic sequencing. The results showed that arecoline promoted lipid metabolism in mice, manifested as significantly reduced serum TC and TG and liver TC levels and a reduction in abdominal fat accumulation. Arecoline intake significantly modulated the neurotransmitters 5-HT and NE levels in the brain. Notably, arecoline intervention significantly increased serum IL-6 and LPS levels, leading to inflammation in the body. High-dose arecoline significantly reduced liver GSH levels and increased MDA levels, which led to oxidative stress in the liver. Arecoline intake promoted the release of intestinal IL-6 and IL-1ß, causing intestinal injury. In addition, we observed a significant response of gut microbiota to arecoline intake, reflecting significant changes in diversity and function of the gut microbes. Further mechanistic exploration suggested that arecoline intake can regulate gut microbes and ultimately affect the host's health. This study provided technical help for the pharmacochemical application and toxicity control of arecoline.

Establishing a novel inflammatory bowel disease prediction model based on gene markers identified from single nucleotide variants of the intestinal microbiota.

The intestinal microbiota is a crucial environmental factor in the development of inflammatory bowel disease (IBD). The abundance of Faecalibacterium prausnitzii is significantly decreased in IBD patients, which is used as a biomarker for IBD diagnosis. However, this can be observed in both IBD and colorectal cancer, which would confound the diagnostic results. Thus, we first established a new model for predicting Crohn's disease (CD) with high precision according to gene characteristics based on single nucleotide variants (SNVs). Next, five gene markers belonging to two species, F. prausnitzii and Eubacterium rectale, that were enriched in the CD group were obtained to build a CD prediction model, and high accuracy in distinguishing the CD and control groups was observed in the discovery (area under curve [AUC] = 91.13%) and validation cohorts (AUC = 79.55%). The model still maintained high accuracy after expanding the healthy cohort (AUC = 89.75%). High disease specificity in distinguishing CD and CRC groups (AUC = 95.74%) was also proven. This study establishes a novel diagnostic method for predicting IBD that also provides unprecedented insight for the early, painless diagnosis of other non-communicable diseases.

Expanding the Colorectal Cancer Biomarkers Based on the Human Gut Phageome.

With the increasing prevalence of colorectal cancer (CRC), extending the present biomarkers for the diagnosis of colorectal cancer is crucial. Previous studies have highlighted the importance of bacteriophages in gastrointestinal diseases, suggesting the potential value of gut phageome in early CRC diagnostic. Here, based on 317 metagenomic samples of three discovery cohorts collected from China (Hong Kong), Austria, and Japan, five intestinal bacteriophages, including Fusobacterium nucleatum, Peptacetobacter hiranonis, and Parvimonas micra phages were identified as potential CRC biomarkers. The five CRC enriched bacteriophagic markers classified patients from controls with an area under the receiver-operating characteristics curve (AUC) of 0.8616 across different populations. Subsequently, we used a total of 80 samples from China (Hainan) and Italy for validation. The AUC of the validation cohort is 0.8197. Moreover, to further explore the specificity of the five intestinal bacteriophage biomarkers in a broader background, we performed a confirmatory meta-analysis using two inflammatory bowel disease cohorts, ulcerative colitis (UC) and Crohn's disease (CD). Excitingly, we observed that the five CRC-enriched phage markers also exhibited high discrimination in UC (AUC = 78.02%). Unfortunately, the five CRC-rich phage markers did not show high resolution in CD (AUC = 48.00%). The present research expands the potential of microbial biomarkers in CRC diagnosis by building a more accurate classification model based on the human gut phageome, providing a new perspective for CRC gut phagotherapy. IMPORTANCE Worldwide, by 2020, colorectal cancer has become the third most common cancer after lung and breast cancer. Phages are strictly host-specific, and this specificity makes them more accurate as biomarkers, but phage biomarkers for colorectal cancer have not been thoroughly explored. Therefore, it is crucial to extend the existing phage biomarkers for the diagnosis of colorectal cancer. Here, we innovatively constructed a relatively accurate prediction model, including: three discovery cohorts, two additional validation cohorts and two cross-disease cohorts. A total of five possible biomarkers of intestinal bacteriophages were obtained. They are Peptacetobacter hiranonis Phage, Fusobacterium nucleatum animalis 7_1 Phage, Fusobacterium nucleatum polymorphum Phage, Fusobacterium nucleatum animalis 4_8 Phage, and Parvimonas micra Phage. This study aims at identifying fine-scale species-strain level phage biomarkers for colorectal cancer diseases, so as to expand the existing CRC biomarkers and provide a new perspective for intestinal phagocytosis therapy of colorectal cancer.

Lactiplantibacillus plantarum HNU082 inhibited the growth of Fusobacterium nucleatum and alleviated the inflammatory response introduced by F. nucleatum invasion.

As a potential biomarker, there is increasing evidence showing that Fusobacterium nucleatum is positively correlated with the occurrence and development of colorectal cancer. Although antibiotics were expected to eliminate F. nucleatum, the side effects associated with gut microbiotal disorders have to be considered. Here, by performing shotgun metagenomic and transcriptome sequencing, we systematically evaluated the antagonistic effects of probiotic Lactiplantibacillus plantarum HNU082 (Lp082) on F. nucleatum in vivo and in vitro. The results showed that the F. nucleatum invasion significantly altered the host intestinal microbiome including the microbial composition, specific species, metabolic pathways and metabolites, as well as impacted the transcriptome of the intestinal epithelial cells. Moreover, the F. nucleatum invasion triggered inflammatory cytokines and inflammatory responses in the intestine but did not develop into colorectal cancer. Excitingly, the Lp082 intervention inhibited the growth of F. nucleatum both in vivo and in vitro and alleviated the inflammatory response introduced by F. nucleatum invasion. Further network-based mechanism exploration demonstrated that Lp082, which negatively correlated to F. nucleatum, maintained the intestinal microbiome homeostasis and prompted the production of beneficial metabolites in the intestine which decreased the expression of inflammatory cytokines in a mouse model. The present research suggested a feasible probiotic intervention strategy for F. nucleatum antagonism in vivo, which may prevent colorectal cancer at the early stage.

Polyphenols in the Fermentation Liquid of Dendrobium candidum Relieve Intestinal Inflammation in Zebrafish Through the Intestinal Microbiome-Mediated Immune Response.

Previous studies of Dendrobium candidum (D. candidum), which is mainly distributed in tropical areas, have mainly focused on its functional polysaccharide; the effects of D. candidum polyphenols, the chemical composition of which may be improved by fermentation, have received limited attention, especially in in vivo models, which inevitably involve interactions with intestinal microorganisms. To address this challenge, metagenomic and metabolomic techniques, were applied, and immune factors and mucosal barrier-related proteins were determined to reveal the effects of fermented D. candidum polyphenols (FDC) on intestinal inflammation induced by oxazolone in zebrafish. The results showed that fermentation significantly changed the chemical composition of D. candidum and that FDC significantly improved the intestinal immune index. After the 21st day of FDC intervention, the abundance of Lactobacillus, Faecalibacterium, and Rummeliibacillus increased, but the abundance of the genera Shewanella, Geodermatophilus, Peptostreptococcaceae, and Mycobacterium decreased. At the same time, FDC significantly increased intestinal short-chain fatty acids (SCFAs). In addition, network analysis based on multi-omics indicated that FDC intake leads to changes in intestinal microbiota and intestinal metabolites, resulting in enhanced host immune function. These results indicate that FDC can improve intestinal health by regulating the intestinal microbiota and its metabolites to treat intestinal inflammation and regulate the host immune system. The present research improved our understanding of the utilization of D. candidum polyphenols and provided new evidence for the impacts of fermented D. candidum on host health.

Potassium sorbate suppresses intestinal microbial activity and triggers immune regulation in zebrafish (Danio rerio).

Potassium sorbate (PS) is a class of bacteriostatic antiseptic agent widely used in the food industry; the effects of its intake on host health are currently unclear. In the present study, zebrafish (Danio rerio) were exposed to 0.1 g L-1 and 1 g L-1 aqueous solutions of PS for 2 weeks to investigate the impact of PS on the microecological balance of the intestinal microbiota and immune system. PS exposure triggered immune regulation of zebrafish, significantly reducing the content of diverse biomarkers in the gut, including Immunoglobulin G (IgG), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Based on high-throughput sequencing data, it was observed that PS exposure resulted in some destabilization of the microbiome composition of the zebrafish, which mainly manifested as a reduction in the abundance of specific genera and the relative levels of transcription and carbohydrate metabolism related to microbial reproductive ability and activity. These changes were consistent with the activity index of microbiota (AIM), a novel measure that we constructed. Collectively, these results illustrate that PS can affect the immune system of zebrafish by changing the composition and function of the gut microbiota, and inhibiting the metabolism of the intestinal microbiota. Our study offers a new understanding of the toxicity of PS.