The intestinal microbiota represents a diverse population that serves a key role in colorectal cancer (CRC) and its treatment outcomes. Advancements in sequencing have revealed notable shifts in microbial composition and diversity among individuals with CRC. Concurrently, animal models have elucidated the involvement of specific microbes such as Lactobacillus fragilis, Escherichia coli and Fusobacterium nucleatum in the progression of CRC. The present review aimed to highlight contributions of intestinal microbiota to the pathogenesis of CRC, the effects of traditional treatments on intestinal microbiota and the potential for microbiota modulation as a therapeutic strategy for CRC.

A gastric ulcer is a stomach lining or nearby intestine disruption caused by acid and pepsin. Helicobacter pylori (H. pylori) and NSAIDs are the primary culprits behind stomach infections that can lead to gastric ulcers and other digestive disorders. Additionally, lifestyle choices such as alcohol consumption and cigarette smoking, stress, and exposure to cold environments can also contribute to non-infectious gastric ulcers. Various treatments are available for gastric ulcers, including antibiotics, anticholinergics, and antacids. However, potential concerns include antibiotic resistance, side effects, and treatment failure. Considering this, there is a need for an alternative approach to manage it. Fortunately, probiotics, typically Lactobacillus and Bifidobacterium, show potential for healing gastric ulcers, offering a non-invasive alternative to conventional treatments. A notable concern arises from applying probiotic bacteria stemming from the propensity of pathogenic bacteria to develop antimicrobial resistance in response to antibiotic therapies. Therefore, the use of yeast becomes more imperative due to its natural resistance to antibacterial antibiotics for antibacterial-treated patients. Probiotic bacteria and yeasts could heal gastric ulcers by regulating the immune response, reducing inflammation, and restoring the balance between defensive and aggressive factors of the gastric layer. This comprehensive review provides an in-depth analysis of the benefits of probiotics and their potential as a therapeutic treatment for non-infectious gastric ulcers, along with other probiotic options. In particular, this review provides a succinct summary of multiple literature studies on probiotics, emphasising the distinctive properties of yeast probiotics, as well as their (bacteria and yeasts) application in the management of non-infectious gastric ulcers.

Dysbiosis is a clinical condition marked by altered gut microbiota resulting from external and internal host factors. It is strongly associated with gastrointestinal and extraintestinal alterations, so its symptomatology is broad and nonspecific. To date, gaps remain that limit professionals from making a timely diagnosis and prescribing the appropriate treatment. We aim to synthesize existing literature regarding clinical parameters for the early detection of patients with intestinal dysbiosis and the clinical events in which the use of probiotics as adjuvant therapy is most frequently reported. A scoping review of the literature was conducted in PubMed, Embase, Cochrane, and BVS (Biblioteca Virtual en Salud in Spanish) databases for articles published in the last 5 years. Primary studies and literature reviews related to clinical presentation, dysbiosis screening, and probiotics as adjuvant therapy for adult and pediatric patients were included. Twenty-three articles were retrieved in which the most frequently reported symptoms were abdominal distension, abdominal pain, and diarrhea. Chronic and metabolic diseases where the conditions most strongly associated with dysbiosis. Depending on symptomatology and etiology, dysbiosis is often treated with probiotics. Dysbiosis, often linked to diarrhea, should be considered with other symptoms like abdominal distension and pain, along with predisposing conditions and patient risk factors. Probiotics are commonly used as co-adjuvant treatments for antibiotic-associated diarrhea, irritable bowel syndrome, and childhood allergic diseases. The most commonly used probiotics were Weizmannia coagulans (formerly B. coagulans), Alkalihalobacillus clausii (formerly Bacillus clausii), Lacticaseibacillus rhamnosus, Limosilactobacillus reuteri, and Saccharomyces boulardii.

Sepsis remains a life-threatening condition with high mortality rates despite current therapeutic approaches. While Huang-Lian-Jie-Du Decoction (HLJDD), a traditional Chinese medicine formula, has been historically used to treat inflammatory conditions, its therapeutic potential in sepsis and underlying mechanisms remain unexplored. This study investigated HLJDD's comprehensive effects on sepsis pathophysiology using a rat cecal ligation and puncture (CLP) model. HLJDD significantly improved survival rates and demonstrated sophisticated immunomodulatory effects through temporal regulation of the biphasic immune response characteristic of sepsis. In early sepsis, HLJDD suppressed pro-inflammatory cytokines (IL-1β, IL-6) while maintaining defensive inflammation. During late sepsis, it counteracted immunosuppression by reducing IL-10 levels and CD4+CD25+ T cell populations while protecting CD4+ and CD8+ T cells from apoptosis. Notably, HLJDD demonstrated dynamic regulation of the gut microbiota-metabolite axis. It enhanced beneficial bacterial populations (Firmicutes, Lactobacillus) while suppressing potentially pathogenic species (Bacteroides, Parabacteroides). Metabolomic analysis revealed time-dependent modulation of short-chain fatty acids, with elevated levels at 12 h followed by strategic reduction at 18-30 h, coordinating with changes in SCFA-producing bacteria. This temporal metabolic regulation corresponded with improved intestinal barrier function and balanced immune responses. The study unveils HLJDD's novel mechanism of action through synchronized modulation of immune responses, gut microbiota, and metabolite profiles, presenting a multi-target therapeutic approach that addresses the complex pathophysiology of sepsis. These findings provide a strong foundation for further clinical investigation of HLJDD as an innovative treatment strategy for sepsis.

Weizmannia coagulans has been shown to have anticancer properties. However, there is limited research on the effects of postbiotic W. coagulans on colorectal cancer cell proliferation. Additionally, the exact mechanisms through which it influences apoptosis- and autophagy-related signaling pathways are yet to be thoroughly elucidated. This study explored the role of W. coagulans MZY531 as a postbiotic in inhibiting tumor growth by modulating apoptosis and autophagy in tumor cells. During the experimental period in the model group, tumors proliferated, tumor markers increased significantly, and immunofluorescence results showed that caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling were significantly decreased. Conversely, supplementation with W. coagulans MZY531 postbiotics significantly reduced the levels of tumor markers carcinoembryonic antigen, colon cancer antigen, and extracellular protein kinase A and promoted cell apoptosis by increasing the caspase-3-positive count and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in tumor tissue. Mechanistically, W. coagulans MZY531 postbiotics inhibit tumor growth through the modulation of the Bax/Bcl-2/caspase-3 and JAK2/STAT3 apoptosis pathways and PI3K/AKT/mTOR and TGF-β/SMAD4 cell autophagy pathways. W. coagulans MZY531 postbiotics had a more significant effect than that of W. coagulans MZY531 alone. Probiotics are expected to become effective natural functional foods for the treatment of colorectal cancer.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

In this article, we review the most recent research on probiotics effects on diarrhea in both human and animal models of the condition along with the therapeutic potential of these compounds based on their findings.

Nearly 50%-80% of cancer patients experience chemotherapy-induced diarrhea (CID), serious gastrointestinal toxicity of chemotherapeutic and radiation regimens that leads to prolonged hospitalizations, cardiovascular problems, electrolyte imbalances, disruptions in cancer treatment, poor cancer prognosis, and death. CID is typically categorized as osmotic diarrhea. The depletion of colonic crypts and villi by radiotherapy and chemotherapy agents interferes with the absorptive function of the intestine, thereby decreasing the absorption of chloride and releasing water into the intestinal lumen. Probiotic supplements have been found to be able to reverse the intestinal damage caused by chemo-radiation therapy by promoting the growth of crypt and villi and reducing inflammatory pathways. In addition, they support the modulation of immunological and angiogenesis responses in the gut as well as the metabolism of certain digestive enzymes by altering the gut microbiota.

Beyond the benefits of probiotics, additional clinical research is required to clarify the most effective strain combinations and dosages for preventing chemotherapy and radiotherapy diarrhea.

Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food "Jiangshui", exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer Lachnospiraceae NK4A136 group and suppressing pro-inflammatory strain Bacteroides. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (xseA, ALDH) and butyrate synthesis gene (bcd), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.

The regulation of neurogenesis, the complex process of producing and differentiating new brain tissue cells, is influenced by a complex interaction of internal and external factors. Over the past decade, extensive research has been conducted on neurotrophins and their key role in adult neurogenesis, as well as their impact on diseases such as depression. Among neurotrophins, the brain-derived neurotrophic factor (BDNF) has been the subject of comprehensive studies on adult neurogenesis, and scientific evidence supports its necessity for neurogenesis in the subventricular zone of the hippocampus. A novel area of research is the emerging role of gut microbiota as a significant contributor to neurogenesis and neurotrophin production. Studies have shown that reduced BDNF levels can lead to mood disorders, which are observed in intestinal dysbiosis, characterized by an imbalance in the composition and quantity of the intestinal microbiota. There is evidence in the literature that there is a link between brain function and gut microbiota. Physical activity, and especially the regularity and intensity of exercise, is important in relation to the level of BDNF and the intestinal microbiota. Probiotics, prebiotics and physical activity may have a positive effect on the intestinal microbiota, and therefore also on the level of the brain-derived neurotrophic factor.

Colorectal cancer (CRC), the third most common cancer worldwide, develops mainly due to the accumulation of genetic and epigenetic changes over many years. Substantial evidence suggests that gut microbiota plays a significant role in the initiation, progression, and control of CRC, depending on the balance between beneficial and pathogenic microorganisms. Nonetheless, gut microbiota composition by regulating the host immune response may either promote or inhibit CRC. Thus, modification of gut microbiota potentially impacts clinical outcomes of immunotherapy. Previous studies have indicated that therapeutic strategies such as probiotics, prebiotics, and postbiotics enhance the intestinal immune system and improve the efficacy of immunotherapeutic agents, potentially serving as a complementary strategy in cancer immunotherapy. This review discusses the role of the gut microbiota in the onset and development of CRC in relation to the immune response. Additionally, we focus on the effect of strategies manipulating gut microbiome on the immune response and efficacy of immunotherapy against CRC. We demonstrate that manipulation of gut microbiome can enhance immune response and outcomes of immunotherapy through downregulating Treg cells and other immunosuppressive cells while improving the function of T cells within the tumor; however, further research, especially clinical trials, are needed to evaluate its efficacy in cancer treatment.

Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled.

To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.

Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.

The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones.

These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression.

In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UV- killed B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR.

Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group.

The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC.

Fermented foods can provide many benefits to our health. These foods are created by the action of microorganisms and help support our digestive health and immune system. Fermented foods include yogurt, kimchi, pickles, kefir, beer, wine, and more. Fermented foods contain probiotics, lactic acid bacteria (LAB), yeast, organic acids, ethanol, or antimicrobial compounds, which help balance the gut microbiome and improve digestive health. Fermented foods can also benefit your overall health by increasing the diversity of your gut microbiome and reducing inflammation. By routinely consuming fermented foods with these benefits, we can continue to improve our health. Probiotics from fermented foods are beneficial strains of bacteria that are safe for human health and constitute an important component of human health, even for children and the elderly. Probiotics can have a positive impact on your health, especially by helping to balance your gut microbiome and improve digestive health. Probiotics can also boost your immune system and reduce inflammation, which can benefit your overall health. Probiotics, which can be consumed in the diet or in supplement form, are found in many different types of foods and beverages. Research is continuing to investigate the health effects of probiotics and how they can be utilized. The potential mechanisms of probiotics include anti-cancer activity, preventing and treating immune system-related diseases, and slowing the development of Alzheimer's disease and Huntington's disease. This is due to the gut-brain axis of probiotics, which provides a range of health benefits beyond the digestive and gastrointestinal systems. Probiotics reduce tumor necrosis factor-α and interleukins through the nuclear factor-kappa B and mitogen-activated protein kinase pathways. They have been shown to protect against colon cancer and colitis by interfering with the adhesion of harmful bacteria in the gut. This article is based on clinical and review studies identified in the electronic databases PubMed, Web of Science, Embase, and Google Scholar, and a systematic review of clinical studies was performed.

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p < 0.001; I2=79.0%, p < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p < 0.001; I2= 48.8%, p < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p < 0.001; I2=44.4%, p = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p < 0.001; I2=31.3%, p = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p < 0.001; I2=95.5%, p < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72 p < 0.001; I2=22.1%, p = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p < 0.001; I2=90.7%, p < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p < 0.001; I2=0.00%, p = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

Colorectal cancer (CRC) is one of the most common malignancies and the leading causes of cancer related deaths worldwide. The development of CRC is driven by a combination of genetic and environmental factors. There is growing evidence that changes in dietary nutrition may modulate the CRC risk, and protective effects on the risk of developing CRC have been advocated for specific nutrients such as glucose, amino acids, lipid, vitamins, micronutrients and prebiotics. Metabolic crosstalk between tumor cells, tumor microenvironment components and intestinal flora further promote proliferation, invasion and metastasis of CRC cells and leads to treatment resistance. This review summarizes the research progress on CRC prevention, pathogenesis, and treatment by dietary supplementation or deficiency of glucose, amino acids, lipids, vitamins, micronutri-ents, and prebiotics, respectively. The roles played by different nutrients and dietary crosstalk in the tumor microenvironment and metabolism are discussed, and nutritional modulation is inspired to be beneficial in the prevention and treatment of CRC.

This review examines the techno-functional properties of lactic acid bacteria (LABs) in the food industry, focusing on their potential health benefits. We discuss current findings related to the techno-functionality of LAB, which includes acidification, proteolytic and lipolytic features, and a variety of other biochemical activities. These activities include the production of antimicrobial compounds and the synthesis of exopolysaccharides that improve food safety and consumer sensory experience. LABs are also known for their antioxidant abilities, which help reduce oxidative reactions in foods and improve their functional properties. In addition, LABs' role as probiotics is known for their promising effects on gut health, immune system modulation, cholesterol control, and general wellbeing. Despite these advantages, several challenges hinder the effective production and use of probiotic LABs, such as maintaining strain viability during storage and transport as well as ensuring their efficacy in the gastrointestinal tract. Our review identifies these critical barriers and suggests avenues for future research.

The effectiveness of the supplementation of prebiotics, probiotics and synbiotics as a therapeutic approach in colorectal cancer (CRC) remains unclear. The aim of this systematic review is to critically examine the current scientific evidence on the impact of modulating the microbiota, through the use of prebiotics, probiotics and synbiotics, in patients diagnosed with CRC undergoing treatment, to determine the potential therapeutic use of this approach.

This systematic review was made according to the PRISMA 2020 guidelines. Inclusion criteria were randomized controlled trials (RCT) comparing the impact of pre-, pro-, or synbiotic supplementation with placebo or standard care in patients with CRC undergoing treatment. Exclusion criteria were non-human studies, non-RCTs, and studies in languages other than English or Portuguese. Six databases were consulted, namely, Cochrane Library, Pubmed, Scopus, Cinahl, MedicLatina and Web of Science until May of 2023. RAYYAN software was used to manage the search results and risk of bias was assessed according to the guidelines of the Cochrane Collaboration using the Rob 2.0 tool.

Twenty-four RCTs met the inclusion criteria and were included in this review. Administration of pre-, pro-, or synbiotics improved surgical outcomes such as the incidence of infectious and non-infectious postoperative complications, return to normal gut function, hospital length of stay, and antibiotic usage. The supplementation of these microorganisms also alleviated some symptoms from chemotherapy and radiotherapy, mainly diarrhea. Evidence on the best approach in terms of types of strains, dosage and duration of intervention is still scarce.

Pre-, pro-, and synbiotics supplementation appears to be a beneficial therapeutic approach in CRC treatment to improve surgical outcomes and to alleviate side-effects such as treatment toxicity. More RCTs with larger sample sizes and less heterogeneity are needed to confirm these potential benefits and to determine the best strains, dosage, and duration of administration in each situation.

https://www.crd.york.ac.uk/prospero, identifier CRD42023413958.

Probiotics are defined as "live microorganisms that provide health benefits to the host when administered in adequate amounts." Probiotics have beneficial effects on human health, including antibacterial activity against intestinal pathogens, regulation of blood cholesterol levels, reduction of colitis and inflammation incidence, regulation of the immune system, and prevention of colon cancer. In addition to probiotic bacteria, some phenolic compounds found in foods we consume (both food and beverages) have positive effects on human health. p-coumaric acid (p-CA) is one of the most abundant phenolic compounds in nature and human diet. The interactions between these two different food components (phenolics and probiotics), resulting in more beneficial combinations called synbiotics, are not well understood in terms of how they will affect the gut microbiota by promoting the probiotic properties and growth of probiotic bacteria. Thus, this study aimed to investigate synbiotic relationship between p-CA and Lactobacillus acidophilus LA-5 (LA-5), Lacticaseibacillus rhamnosus GG (LGG). Probiotic bacteria were grown in the presence of p-CA at different concentrations, and the effects of p-CA on probiotic properties, as well as its in vitro effects on AChE and BChE activities, were investigated. Additionally, Surface analysis was conducted using FTIR. The results showed that treatment with p-CA at different concentrations did not exhibit any inhibitory effect on the growth kinetics of LA-5 and LGG probiotic bacteria. Additionally, both probiotic bacteria demonstrated high levels of antibacterial properties. It showed that it increased the auto-aggregation of both probiotics. While p-CA increased co-aggregation of LA-5 and LGG against Escherichia coli, it decreased co-aggregation against Staphylococcus aureus. Probiotics grown with p-CA were more resistant to pepsin. While p-CA increased the resistance of LA-5 to bile salt, it decreased the resistance of LGG. The combinations of bacteria and p-CA efficiently suppressed AChE and BChE with inhibition (%) 11.04-68.43 and 13.20-65.72, respectively. Furthermore, surface analysis was conducted using FTIR to investigate the interaction of p-coumaric acid with LA-5 and LGG, and changes in cell components on the bacterial surface were analyzed. The results, recorded in range of 4000 -600 cm-1 with resolution of 4 cm-1, demonstrated that p-CA significantly affected only the phosphate/CH ratio for both bacteria. These results indicate the addition of p-CA to the probiotic growth may enhance the probiotic properties of bacteria.

Gut microbiota plays a crucial role in modulating immune responses, including effector response to infection and surveillance of tumors. This article summarizes the current scientific evidence on the effects of supplementation with prebiotics, probiotics, and synbiotics on high-risk human papillomavirus (HPV) infections, precancerous lesions, and various stages of cervical cancer development and treatment while also examining the underlying molecular pathways involved. Our findings indicate that a higher dietary fiber intake is associated with a reduced risk of HPV infection, while certain probiotics have shown promising results in clearing HPV-related lesions. Additionally, certain strains of probiotics, prebiotics such as inulin and fructo-oligosaccharides, and synbiotics decrease the frequency of gastrointestinal adverse effects in cervical cancer patients. These agents attain their results by modulating crucial metabolic pathways, including the reduction of inflammation and oxidative stress, promoting apoptosis, inhibiting cell proliferation, and suppressing the activity of oncogenes, thus attenuating tumorigenesis. We conclude that although further human studies are necessary, robust evidence in preclinical models demonstrates that prebiotics, probiotics, and synbiotics play an essential role in cervical cancer, from infection to carcinogenesis and its medical treatment. Consequently, we strongly recommend conducting high-quality clinical trials using these agents as adjuvants since they have proven safe.

Despite the notable advancements witnessed in the past decade in medical and health research domain, cancer remains a prominent global cause of mortality. Moreover, the conventional treatments employed to combat this disease have been found to considerably compromise the quality of life experienced by patients due to its severe side effects. Recent in vitro studies revealed encouraging findings on the potential beneficial effects of probiotics as adjuvants of anticancer therapy, and even as possible agents for the prevention and treatment of various types of malignancies. From this standpoint, the primary objective of this work was to investigate the anticancer properties of Lactiplantibacillus plantarum (LP) and elucidate its underlying mechanism of action. In order to investigate this matter, several doses of LP (ranging from 105 to 1010 CFU/mL) were examined in relation to melanoma cancer cell lines (A375) and breast cancer cell line (MCF-7). The cell viability findings, which were substantiated by morphological investigations and annexin V/PI assay, indicated that LP exerted inhibitory effects on cellular activity and triggered apoptosis. Additionally, upon further investigation into its mechanism, it was observed through the apoptosis assay and Western blot analysis that the administration of LP resulted in an elevation of pro-apoptotic BAX protein levels and an upregulation of cleaved poly-ADP-ribose polymerase (PARP) protein expression. Conversely, the levels of anti-apoptotic Bcl-2 protein were found to decrease in the A375 and MCF-7 cell lines. These findings provide insight into the pro-apoptotic mechanism of action of LP in these specific cell lines.

Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy.

In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment.

This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.

Globally, cancer is among the principal causes of death, and the incidence of colorectal cancer is increasing annually around the world, and it is currently ranked third most diagnosed cancer type. Despite the development in the treatment procedures for colorectal cancer including chemotherapy, surgery, immunotherapy and radiotherapy, the death rates from this cancer type are still elevated due to the adverse effects associated with treatment that may affect patients' quality of life.  Recently, the global interest in probiotics research has grown with significant positive results.  METHODS: This review discusses the role of probiotics in normal colorectal physiology and cancer.

Probiotics will become an essential part in the prevention and management of colorectal cancer in the near future as they are expected to provide a solution to the problems associated with cancer treatment. Probiotics' properties open the way for multiple effective uses in colorectal cancer prevention strategies. Additionally, probiotics can reduce the problems associated with chemotherapy and surgery when used synergistically. Probiotics can also increase the efficacy of chemotherapeutic medications. Targeted drug delivery and TRAIL collaboration techniques are other effective and promising methods that involve probiotics.

Probiotics have properties that make them useful in the management and prevention of colorectal cancer and can provide new avenue to reduce the occurrence of this malignancy and enhance the patients' quality of life.

Scientists are working to identify prevention/treatment methods and clinical outcomes of coronavirus disease 2019 (COVID-19). Nutritional status and diet have a major impact on the COVID-19 disease process, mainly because of the bidirectional interaction between gut microbiota and lung, that is, the gut-lung axis. Individuals with inadequate nutritional status have a pre-existing imbalance in the gut microbiota and immunity as seen in obesity, diabetes, hypertension and other chronic diseases. Communication between the gut microbiota and lungs or other organs and systems may trigger worse clinical outcomes in viral respiratory infections. Thus, this review addresses new insights into the use of probiotics and prebiotics as a preventive nutritional strategy in managing respiratory infections such as COVID-19 and highlighting their anti-inflammatory effects against the main signs and symptoms associated with COVID-19. Literature search was performed through PubMed, Cochrane Library, Scopus and Web of Science databases; relevant clinical articles were included. Significant randomised clinical trials suggest that specific probiotics and/or prebiotics reduce diarrhoea, abdominal pain, vomiting, headache, cough, sore throat, fever, and viral infection complications such as acute respiratory distress syndrome. These beneficial effects are linked with modulation of the microbiota, products of microbial metabolism with antiviral activity, and immune-regulatory properties of specific probiotics and prebiotics through Treg cell production and function. There is a need to conduct clinical and pre-clinical trials to assess the combined effect of consuming these components and undergoing current therapies for COVID-19.

Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.

The CYLD gene is a tumor suppressor, reduced in many cancers. Here, we aimed to investigate CYLD protein level and NF-κβ/TNF-α signaling pathway in rectal cancer patients with Lactobacillus acidophilus (L. acidophilus) consumption. One hundred ten patients with non-metastatic rectal cancer were randomly divided into L. acidophilus probiotic (500 mg, three times daily) and placebo groups for 13 weeks. The expression of CYLD, TNF-α, and NF-κB proteins and the genes involved in the NF-κβ/TNF-α pathway were evaluated using ELISA and qPCR techniques. The survival rate was measured after five years. Unlike the placebo group, the results showed a significant increase in the expression of CYLD protein and tumor suppressor genes, including FOXP3, ROR-γ, Caspase3, GATA3, T-bet, and a considerable decrease in the expression of NF-ҝβ and TNF-α proteins and oncogenes, including STAT3, 4, 5, 6, and SMAD 3, in the probiotic group. A higher overall survival rate was seen after L. acidophilus consumption compared to the placebo group (P < 0.05). L. acidophilus consumption can reduce inflammation factors by affecting CYLD protein and its downstream signaling pathways. A schematic plot of probiotic consumption Effects on the CYLD protein in regulating the NF-ĸβ signaling pathway in colorectal cancer. NF-ĸβ can be activated by canonical and noncanonical pathways, which rely on IκB degradation and p100 processing, respectively. In the canonical NF-κβ pathway, dimmers, such as p65/p50, are maintained in the cytoplasm by interacting with an IκBα protein. The binding of a ligand to a cell-surface receptor activates TRAF2, which triggers an IKK complex, containing -α, -β, -g, which phosphorylates IKK-β. It then phosphorylates IκB-α, leading to K48-ubiquitination and degradation of this protein. The p65/p50 protein freely enters the nucleus to turn on target genes. The non-canonical pathway is primarily involved in p100/RelB activation. It differs from the classical pathway in that only certain receptor signals activate this pathway. It proceeds through an IKK complex that contains two IKK-α subunits but not NEMO. Several materials including peptidoglycan, phorbol, myristate, acetate, and gram-positive bacteria such as probiotics inhibit NF-κB by inducing CYLD. This protein can block the canonical and noncanonical NF-κβ pathways by removing Lys-63 ubiquitinated chains from activated TRAFs, RIP, NEMO, and IKK (α, β, and γ). Moreover, TNF-α induces apoptosis by binding caspase-3 to FADD.

This study aimed to compare the effects of the probiotic bacteria, L. gasseri (52b), L. plantarum (M11), L. acidophilus (AC2), and L. fermentum (19SH), isolated from human source and traditional food products on the modulation of the immune system and inflammatory response on BALB/c mouse model bearing CT26 tumor. Five groups of female inbred BALB/c mice were orally administered with the probiotics and their mixes (MIX, at a 1:1 ratio) at varying dosages (1.5 × 108 cfu/ml and 1.2 × 109 cfu/ml) before and after the injection of a subcutaneous CT26 tumor over the course of 38 days via gavage. Finally, their effects on the tumor apoptosis and the cytokine levels in spleen cell cultures were analyzed and compared. M11, MIX, and 52b groups had the greatest levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) production. The highest production level of granzyme B (GrB) was related to the MIX and 52b groups. Moreover, these groups showed the lowest production level of (IL-4) and transforming growth factor beta (TGF-β). Furthermore, the groups of MIX and 52b demonstrated the greatest amount of lymphocyte proliferation of spleen cells in response to the tumor antigen. The delayed-type hypersensitivity (DTH) response significantly increased in the groups of MIX and 52b compared with the control (p < 0.05). The findings demonstrated that the oral treatment of the human strain (52b) and the combination of these bacteria generated strong T helper type 1 (Th1) immune responses in the tumor tissue of the tumor-bearing mice, which led to the suppression of the tumor development.

Colorectal cancer (CRC) is the third most common cancer in the world, and its incidence rate and mortality are on the rise in many countries. In recent years, with the improvement of economic conditions, people's living habits have changed, including lack of physical activity, poor diet patterns and circadian rhythm disorder. These risk factors can change the colon environment and the composition of intestinal microbiota. This state is called intestinal imbalance, which increases the risk of cancer. Probiotics, a class of microorganisms that help maintain gut microbial homeostasis and alleviate dysbiosis, may help prevent inflammation and colorectal cancer. These probiotics inhibit or ameliorate the effects of dysbiosis through the production of short-chain fatty acids (SCFAs), modulation of immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other mechanisms. This review aims to explain the interaction between probiotics, the gut microenvironment and the gut microbiota, and summarize reports on the possibility of probiotics in the prevention and treatment of colorectal cancer.

Titanium dioxide (TiO2) is a common additive in foods, medicines, and personal care products. In recent years, nano-scale particles in TiO2 additives have been an increasing concern due to their potential adverse effects on human health, especially gut health. The objective of this study was to determine the impact of titanium dioxide nanoparticles (TiO2 NPs, 30 nm) on beneficial gut bacteria and host response from a metabolomics perspective. In the in vitro study, four bacterial strains, including Lactobacillus reuteri, Lactobacillus gasseri, Bifidobacterium animalis, and Bifidobacterium longum were subjected to the treatment of TiO2 NPs. The growth kinetics, cell viability, cell membrane permeability, and metabolomics response were determined. TiO2 NPs at the concentration of 200 μg/mL showed inhibitory effects on the growth of all four strains. The confocal microscope results indicated that the growth inhibitory effects could be associated with cell membrane damage caused by TiO2 NPs to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health. In the in vivo study, mice were fed with TiO2 NPs (0.1 wt% in diet) for 8 weeks. Mouse urine was collected for metabolomics analysis and the tryptophan metabolism pathway was also significantly affected in TiO2 NPs-fed mice. Moreover, four neuroprotective metabolites were significantly reduced in both in vitro bacteria and in vivo urine samples. Overall, this study provides insights into the potential adverse effects of TiO2 NPs on gut bacteria and the metabolic responses of both bacteria and host. Further research is needed to understand the causality between gut bacteria composition and the metabolism pathway, which is critical to monitor the gut-microbiome mediated metabolome changes in toxicological assessment of food components.

The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These relationships can alter all aspects of drug pharmacokinetics and pharmacodynamics (PK/PD); thus, there is a desire to control these interactions to maximize therapeutic efficacy. Attempts to modulate drug-gut microbiome interactions have spurred advancements within the field of 'pharmacomicrobiomics' and are poised to become the next frontier of oral drug delivery.

This review details the bidirectional interactions that exist between oral drugs and the gut microbiome, with clinically relevant case examples outlining a clear motive for controlling pharmacomicrobiomic interactions. Specific focus is attributed to novel and advanced strategies that have demonstrated success in mediating drug-gut microbiome interactions.

Co-administration of gut-active supplements (e.g. pro- and pre-biotics), innovative drug delivery vehicles, and strategic polypharmacy serve as the most promising and clinically viable approaches for controlling pharmacomicrobiomic interactions. Targeting the gut microbiome through these strategies presents new opportunities for improving therapeutic efficacy by precisely mediating PK/PD, while mitigating metabolic disturbances caused by drug-induced gut dysbiosis. However, successfully translating preclinical potential into clinical outcomes relies on overcoming key challenges related to interindividual variability in microbiome composition and study design parameters.

To explore the role of Huangqin Decoction in intestinal homeostasis maintenance and colon carcinogenesis based on "sterol regulatory element binding protein-1c (SREBP-1)-cholesterol metabolism regulatory T cell (Treg) differentiation."

It was decided to utilize a total of 50 healthy Wistar rats for the study, 20 of which were chosen at random to serve as controls, and 30 of which were used to create an intestinal homeostasis imbalance model. It was determined whether or not the modeling was successful by killing 10 rats from each of the two groups. The remaining 10 rats in the normal group were then employed as the control group for the experiment. The random number table method was used to split the rats into two groups: the Huangqin Decoction (n = 10) and the Natural Recovery (n = 10) groups. For seven days, participants in the Huangqin Decoction group received the herb, whereas those in the natural healing group received normal saline. The relative density of SREBP1, the levels of cholesterol ester (CE), free cholesterol (FC), total cholesterol (TC), and Treg cells were detected and compared.

When compared to the control group, the relative density of SREBP1 increased significantly before administration in the Huangqin Decoction group and the natural recovery group, but decreased significantly after administration, with statistical significance (P < 0.05) in the Huangqin Decoction group and the natural recovery group; the Huangqin Decoction group and natural recovery group had significantly higher levels of CE, FC, and TC than the control group before to administration, and these levels increased significantly after administration. CE, FC, and TC levels in Huangqin Decoction and natural recovery groups were much lower than those in natural recovery groups, and the difference was statistically significant (P < 0.05), according to the results; Prior to administration, Treg cell levels in Huangqin Decoction group and the natural recovery group were significantly higher, and Treg cell levels in the Huangqin Decoction group and natural recovery group were significantly lower after administration; the decrease in the Huangqin Decoction group was significantly greater than that in natural recovery group. P < 0.05 indicated that the difference was significant.

Using Huangqin Decoction, one may efficiently regulate SREBP1, cholesterol metabolism, and Treg cell development, all of which play an important role in maintaining intestinal stability and minimizing the incidence of colon cancer.

Preliminary studies have identified the use of probiotics as a potential treatment strategy against colorectal cancer (CRC). However, natural probiotics lack direct tumor-targeting and tumor-killing activity in the intestine. This study aimed to construct a tumor-targeting engineered probiotic to combat CRC.

Standard adhesion assay was performed to analyze the adherence ability of tumor-binding protein HlpA to CT26 cells. CCK-8 assay, Hoechst 33258 staining and flow cytometry analysis were used for examining cytotoxicity of tumoricidal protein azurin toward CT26 cells. An engineered probiotic Ep-AH harboring azurin and hlpA genes was developed using Escherichia coli Nissle 1917 (EcN) chassis. Antitumor effects of Ep-AH were evaluated in the azoxymethane (AOM) and dextran sodium sulfate salt (DSS)-induced CRC mice. Moreover, analysis of gut microbiota was conducted via fecal 16S rRNA gene sequencing and shotgun metagenomic sequencing.

Azurin caused a dose-dependent increase of apoptosis in CT26 cells. Ep-AH treatment reversed weight loss (p < 0.001), fecal occult blood (p < 0.01), and shortening of colon length (p < 0.001) than model group, as well as reducing tumorigenesis by 36 % (p < 0.001). Both Ep-H and Ep-A (EcN expressing HlpA or azurin) were less effective than Ep-AH. Furthermore, Ep-AH enriched the members of beneficial bacteria (e.g., Blautia and Bifidobacterium) and reversed abnormal changes of genes associated with several metabolic pathways (e.g., lipopolysaccharide biosynthesis).

These results demonstrated that Ep-AH had excellent therapeutic benefits on cancer remission and gut microbiota modulation. Our study provides an effective strategy for anti-CRC treatment.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

Gut microbiota is considered as a complex organ of human body. The interaction between the host and microbiota is dynamic and controlled by a huge number of factors, such as lifestyle, geography, pharmaceuticals, diet, and stress. The breakdown of this relationship could change microbiota composition favoring the onset of several diseases, including cancer. Metabolites released by microbiota bacterial strains have been reported to elicit protective effects on the mucosa that could contrast cancer development and progression. Here, we tested the ability of specific probiotic strain Lactiplantibacillus plantarum OC01-derived metabolites (NCIMB 30624) to contrast the malignant features of colorectal cancer (CRC) cells.

The study was performed on two cell lines, HCT116 and HT29, cultured in 2D and 3D, and focused on the hallmarks of cell proliferation and migration.

Probiotic metabolites reduced cell proliferation both in 2D and 3D-spheroid cultures, the latter model mimicking the growth in vivo. The bacterial metabolites also contrasted the pro-growth and pro-migratory activity of inteurleukin-6 (IL-6), an inflammatory cytokine abundantly found in the tumor microenvironment of CRC. These effects were associated with inhibition of the ERK and of the mTOR/p70S6k pathways and with the inhibition of the E-to N-Cadherin switch. In a parallel study, we found that sodium butyrate (a representative of the main probiotic metabolites) induced autophagy and β-Catenin degradation, which is consistent with the growth inhibitory activity. The present data indicate that the metabolites of Lactiplantibacillus plantarum OC01 (NCIMB 30624) elicits anti-tumor effect and support its possible inclusion as adjuvant therapy of CRC for limiting cancer growth and progression.

In this work, the effects of probiotic supplementation on cisplatin toxicity in zebrafish (Danio rerio) were examined. For this study, adult female zebrafish were given cisplatin (G2), the probiotic, Bacillus megaterium (G3), and cisplatin+B. megaterium (G4) for 30 days, in addition to the control (G1). In order to investigate changes in antioxidative enzymes, ROS production, and histological changes after treatment, the intestines and ovaries were excised. The levels of lipid peroxidation, glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase were found to be significantly higher in the cisplatin group than in the control group in both the intestine and the ovaries. Administration of the probiotic and cisplatin effectively reversed this damage. Histopathological analyses showed that the cisplatin group had much more damage than the control group and that probiotic+cisplatin treatment significantly cured these damages. It opens the door to probiotics being combined with cancer-related drugs, which may be a more efficient approach for minimizing side effects. The underlying molecular mechanisms of probiotics must be further investigated.

Colorectal cancer (CRC) is the third most common type of cancer, posing a serious threat to human life. It is widely believed that dietary factors may be crucial modifiers of CRC risk, with pro-and/or prebiotics being especially promising. In this review, a synthesis of CRC prevention and treatment of strategies relying on usage of pro- and/or prebiotics supplements is given, as well as discuss mechanisms underlying the contribution of pro-and/or prebiotics to the suppression of colonic carcinogenesis. Furthermore, a framework for personalizing such supplements according to the composition of an individual's gut microbiome is suggested. Various factors including diversity of one's intestinal microflora, integrity of their intestinal barrier, and the presence of mutagenic/carcinogenic/genotoxic and beneficial compounds are known to have a prominent influence on the development of CRC; thus, clarifying the role of pro- and/or prebiotics will yield valuable insight toward optimizing interventions for enhanced patient outcomes in the future.

Fusobacterium nucleatum is involved in the development and progression of colorectal cancer. Although the gut microbiota is influenced by diet, studies on the association between diet and F. nucleatum are limited. We aimed to evaluate the association between various dietary factors and fecal F. nucleatum in healthy adults without a history of colorectal cancer or precancerous lesions. This was a cross-sectional study. Subjects who underwent total colonoscopy at the National Cancer Center Hospital (Tokyo, Japan) were included. Healthy subjects (n = 212) were divided into two groups according to the presence or absence of F. nucleatum in their feces which was calculated from data of whole-genome shotgun sequencing, with the group with F. nucleatum serving as cases and the group without F. nucleatum serving as controls. Multivariable logistic regression analysis adjusted potential confounders was conducted to estimate the associations between dietary intake and nutrients estimated by a validated food frequency questionnaire and the presence of F. nucleatum in the feces. There was a significant inverse association between dairy products and the presence of fecal F. nucleatum [high vs. low; OR, 0.41; 95% confidence interval, 0.17-0.95; Ptrend, 0.039]. These results may have important implications for colorectal cancer prevention through nutritional intervention.

F. nucleatum is well known as a colorectal cancer-associated bacterium. Dietary habits alter the composition and function of the intestinal microbiota. A high intake of dairy products in healthy adults may reduce F. nucleatum and prevent colorectal cancer.

Diversity and composition of the gut microbiome are associated with cancer patient outcomes including colorectal cancer (CRC). A growing number of evidence indicates that Fusobacterium nucleatum (Fn) in CRC tissue is associated with worse survival. However, few studies have further analyzed the differences in bacteria in tumor tissues of different patients depending on the survival time of CRC patients. Therefore, there is a need to further explore the bacterial differences in tumor tissues of patients with different prognoses and to identify key bacteria for analysis. Here, we sought to compare the differences in tumor microbiome between patients with long-term survival (LS) longer than 3 years or 4 and 5 years and patients with short-term survival (SS) in the present study cohort. We found that there were significant differences in tumor microbiome between the LS and SS and two bacteria-Caulobacter and Novosphingobium-that are present in all of the three groups. Furthermore, by analyzing bacteria in different clinical features, we also found that lower levels of microbiome (Caulobacter and Novosphingobium) have long-term survival and modulating microbiome in tumor tissue may provide an alternative way to predict the prognosis of CRC patients.

Clinical oncology has shown outstanding progress improving patient survival due to the incorporation of new drugs. However, treatment success may be reduced by the emergency of dose-limiting side effects, such as intestinal mucositis and diarrhea. Mucositis and diarrhea management is symptomatic, and there is no preventive therapy. Bacterial and fungal-based compounds have been suggested as an alternative for preventing the development of diarrhea in cancer patients. Using probiotics is safe and effective in immunocompetent individuals, but concerns remain during immunosuppressive conditions. Paraprobiotics, formulations composed of non-viable microorganisms, have been proposed to overcome such limitation. The present literature review discusses current evidence regarding the possible use of paraprobiotics as an alternative to probiotics to prevent gastrointestinal toxicity of cancer chemotherapy.

Colorectal cancer (CRC)is the third most common cancer in the world and the second leading cause of cancer-related deaths, and over the past two decades, many of these researchers have provided a substantial amount of important information on the role of gut microbes in the development and progression of CRC. A causal relationship between the presence of specific microorganisms and CRC development has also been validated. Although a large number of papers related to this area have been published, no bibliometric study has been conducted to review the current state of research in this area and to highlight the research trends and hotspots in this area. This study aims to analyze the current status and future research trends of gut microbiota and CRC through bibliometric analysis.

Publications from 2001 to 2022 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were used to visualize the research trends in this field, including the analysis of title, country, institution, author, number of publications, year of publication, number of citations, journal, and H-index.

A total of 863 studies were eventually identified, and the articles retrieved were cited an average of 44.85 times each. The number of publications on this topic has been increased steadily since 2011. China and the USA have made the largest contribution in the field. FRONTIERS IN MICROBIOLOGY is the top productive journal with 26 papers, and Gut journal has the highest average citation (167.23). Shanghai Jiao Tong University is the most contributive institution. Professor Yu J, Sung, Joseph J. Y and Fang JY are the most productive authors in this field. Keyword co-occurrence analysis showed that the terms of "Gut Microbiota", "Colorectal Cancer", "Inflammation", "Probiotic" and "Fusobacterium Nucleatum" were the most frequent, which revealed the research hotpots and trends in this field.

There has been a growing number of publications over the past two decades according to the global trends. China and the USA still maintained the leading position in this field. However, collaboration between institutions needs to be strengthened. It's commended to pay attention to the latest hotspots, such as "F. nucleatum" and "probiotics". This bibliometric analysis evaluates the scope and trends of gut microbiota and CRC, providing a useful perspective on current research and future directions for studying the link between the gut microbiota and CRC.

Based on the relationship between the gut microbiota and colorectal cancer, we developed a new probiotic powder for treatment of colorectal cancer. Initially, we evaluated the effect of the probiotic powder on CRC using hematoxylin and eosin staining, and evaluated mouse survival rate and tumor size. We then investigated the effects of the probiotic powder on the gut microbiota, immune cells, and apoptotic proteins using 16S rDNA sequencing, flow cytometry, and western blot, respectively. The results showed that the probiotic powder improved the intestinal barrier integrity, survival rate, and reduced tumor size in CRC mice. This effect was associated with changes in the gut microbiota. Specifically, the probiotic powder increased the abundance of Bifidobacterium animalis and reduced the abundance of Clostridium cocleatum. In addition, the probiotic powder resulted in decreased numbers of CD4+ Foxp3+ Treg cells, increased numbers of IFN-γ+ CD8+ T cells and CD4+ IL-4+ Th2 cells, decreased expression of the TIGIT in CD4+ IL-4+ Th2 cells, and increased numbers of CD19+ GL-7+ B cells. Furthermore, the expression of the pro-apoptotic protein BAX was significantly increased in tumor tissues in response to the probiotic powder. In summary, the probiotic powder ameliorated CRC by regulating the gut microbiota, reducing Treg cell abundance, promoting the number of IFN-γ+ CD8+ T cells, increasing Th2 cell abundance, inhibiting the expression of TIGIT in Th2 cells, and increasing B cell abundance in the immune microenvironment of CRC, thereby increasing the expression of BAX in CRC.

Previously, we showed that the growth, antibiotic resistance, and biofilm formation properties of the pathogens Pseudomonas aeruginosa and Klebsiella pneumonia were tremendously inhibited by the cell-free supernatant of the oral probiotic Streptococcus salivarius M18. These anti-pathogenic activities of the supernatant were more efficient under acidic conditions. The present approach takes advantage of the acidic nature of the tumor microenvironment to evaluate the effect of the S. salivarius M18 postbiotics on colon cancer cells. In both two-dimensional (2D) and three-dimensional (3D) cell culture models, S. salivarius M18 cell-free supernatant showed anti-cancer actions in the pH conditions mimicking the acidity of the tumor. The inhibitory effect was more prominent when the colon cancer cells have been treated with the cell-free supernatant obtained from the inulin incubated S. salivarius M18. The results of this study point out the potential of the S. salivarius M18 functional probiotic products to be used for targeting low pH environments including the unique acidic microenvironment of tumors.