The role of intestinal flora on tumorigenesis,progression,and the efficacy of PD-1/PD-L1 antibodies in colorectal cancer

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

Effect of dietary supplementation with discardednutrient medium of Cordyceps militaris on layingperformance and diversity of intestinal flora in laying hens

The aim of the experiment was to explore the feasibility of discarded nutrient medium of Cordyceps militaris as feed in the production of laying hens. 100 g/kg, 200 g/kg, 300 g/kg of discarded nutrient medium of Cordyceps militaris were added to the basal diet of laying hens. The results showed that the optimal addition of discarded nutrient medium of Cordyceps militaris in the diet of laying hens was 10%. According to the results of measuring the conventional indicators of eggs, the weight of eggs produced by laying hens fed with discarded nutrient medium of Cordyceps militaris was higher than that of laying hens fed with ordinary laying hens. The content of interleukin-1(IL-1) in the experimental group was significantly higher than that in the control group, and the concentration of IL-1 increased by 141.5 pg/mL, which indicated that the application of discarded nutrient medium of Cordyceps militaris effectively improved the immunity of laying hens. The high-throughput analysis of the intestinal contents of the two groups of laying hens showed that the microbial population abundance of the intestinal tract of the experimental group was greater than that of control group, and the application of discarded nutrient medium of Cordyceps militaris increased the diversity of bacteria in the intestinal tract of laying hens. In addition, the sensitivity of some pathogenic bacteria in the intestinal tract of chickens to drugs was also increased, thereby reducing the use of antibiotics. The secondary utilization of discarded nutrient medium of Cordyceps militaris has great development and utilization prospects, which provided a scientific reference and basic theoretical basis for the development of discarded nutrient medium of Cordyceps militaris as feed in the production of laying hens.

Intestinal flora: New perspective of type 2 diabetes

Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors.Current diabetes management primarily focuses on blood glucose control,yet it is inherently progressive,necessitating increased reliance on exogenous blood glucose control methods over time.Therefore,there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications.The human intestinal microbiota,often referred to as the"second genome",exhibits significant diversity and plays a pivotal role in insulin resistance,glucose and lipid metabolism,and inflammatory response.Notably,Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus(T2DM)and proposed a novel therapeutic approach targeting intestinal microbes.This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora,thereby offering fresh avenues for understanding its pathogenesis and clinical management.This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies.Additionally,it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery:A propensityscore-matching analysis

BACKGROUND Intestinal flora disorder(IFD)poses a significant challenge after laparoscopic colonic surgery,and no standard criteria exists for its diagnosis and treatment.AIM To analyze the clinical features and risk factors of IFD.METHODS Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching(PSM)methods.Based on the occurrence of IFD,patients were categorized into IFD and non-IFD groups.The clinical characteristics and treatment approaches for patients with IFD were analyzed.Multivariate regression analysis was performed to identify the risk factors of IFD.RESULTS The IFD incidence after laparoscopic surgery was 9.0%(97 of 1073 patients).After PSM,97 and 194 patients were identified in the IFD and non-IFD groups,respectively.The most common symptoms of IFD were diarrhea and abdominal,typically occurring on post-operative days 3 and 4.All patients were managed conservatively,including modulation of the intestinal flora(90.7%),oral/intravenous application of vancomycin(74.2%),and insertion of a gastric/ileus tube for decompression(23.7%).Multivariate regression analysis identified that preoperative intestinal obstruction[odds ratio(OR)=2.79,95%CI:1.04–7.47,P=0.041]and post-operative antibiotics(OR=8.57,95%CI:3.31–23.49,P<0.001)were independent risk factors for IFD,whereas pre-operative parenteral nutrition(OR=0.12,95%CI:0.06–0.26,P<0.001)emerged as a protective factor.CONCLUSION A stepwise approach of probiotics,vancomycin,and decompression could be an alternative treatment for IFD.Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.

Effects of Compound Probiotics on Growth Performance and Intestinal Flora of Kunming Mice

[Objectives]This study was conducted to investigate the effects of adding compound probiotics on the growth performance and intestinal flora of Kunming mice.[Methods]Twelve healthy 2-week-old Kunming male mice with body weight of(11.09±0.43)g were selected.They were randomly divided into two treatment groups,namely blank control group(NC)and compound probiotics group(CB+LR+BS),with six mice in each group.The two groups were fed with commercial basal diet,and the compound probiotic experimental group was fed with basal diet supplemented with compound probiotics,in which the contents of Clostridium butyricum spores,Lactobacillus reuteri and Bacillus subtilis spores were 1×1010,1×1011 and 1×1010 CUF/kg,respectively.The body weight,feed intake and water intake of mice were counted every 4 d,and the experimental period was 13 d.On the 13 th day,the cecal contents of the mice were collected for analysis.[Results]There was no significant change in body weight and feed intake when compound probiotics were added to the diet.However,the addition of compound probiotics reduced the abundance of harmful bacteria such as Escherichia coli,urease-negative Helicobacter typhlonius and Salmonella enterica,while increasing the abundance of beneficial bacteria such as Anaerostipes hadrus,and the contents of IgG and IgM increased significantly(P<0.05).[Conclusions]In summary,the addition of compound probiotics could significantly improve the structure of intestinal microbial flora,increase the quantity of beneficial bacteria,reduce the quantity of harmful bacteria,and improve the immune function of mice.

Research Progress of Intestinal Flora in Colorectal Cancer

Colorectal cancer, as a common malignant tumor, has been increasing in incidence year by year and has become one of the leading causes of death worldwide. Meanwhile, researchers have found a close relationship between dysbiosis of the gut microbiota and colorectal cancer, which has further triggered indepth exploration of the role of gut microbiota in the pathogenesis, diagnosis, and treatment of colorectal cancer. Studies have shown that there are specific microbial changes in colorectal cancer tissues, including enrichment or depletion of certain bacterial species, which may be associated with tumor growth, invasion, and metastasis. Additionally, gut microbiota has been found to be closely linked to tumor microenvironment, tumor immune response, chemotherapy drug metabolism, and other factors. In this context, it is imperative to study the gut microbiota in colorectal cancer. A comprehensive understanding of the interaction between gut microbiota and colorectal cancer is not only helpful in revealing novel mechanisms of colorectal cancer development, but also holds promise in providing new strategies and targets for early diagnosis, individualized treatment, and prevention of colorectal cancer. This review aims to thoroughly discuss the research progress of gut microbiota in colorectal cancer, including its compositional characteristics, its role in the occurrence and development of colorectal cancer, and its potential clinical applications. The goal is to provide references and insights for further research in this field.

Correlation Analysis Between Children with Atopic Dermatitis and Asthma and Factors Affecting Intestinal Flora

Objective:In order to reveal the potential association between intestinal flora and atopic dermatitis with asthma,the study compares the changes in intestinal flora before and after treatment with antibiotics in children and explores the risk factors for the disease development in children.The differences between asthma-controlled children and healthy children were also analyzed to investigate whether there was a correlation between the level of control and intestinal flora in asthmatic children.Methods:367 children with atopic dermatitis and asthma were selected,and the control group was healthy children who did not have other skin diseases.Fecal samples were collected from healthy children and children with asthma,and the intestinal flora was tested at Beijing Nebula Medical Testing Laboratory Co.At the same time,50 children were selected according to the inclusion and exclusion criteria to take amide antibiotics during hospitalization,and stool samples were collected before and after taking antibiotics.Results:The proportion of Gram-positive cocci increased and the proportion of Gram-positive bacilli decreased after the administration of antibiotics in children with atopic dermatitis and asthma(P<0.05),and no significant difference was shown in the gender and age of the children(P>0.05).The proportion of family history of atopic dermatitis with asthma was higher in the experimental group(P<0.05).Conclusion:The use of antibiotics in children with atopic dermatitis with asthma showed a positive correlation with changes in intestinal flora.The use of antibiotics may lead to changes in intestinal flora and increase the risk of atopic dermatitis with asthma.Antibiotic use in infancy and childhood is also recognized as a risk factor for atopic dermatitis with asthma.Therefore,the use of antibiotics should be minimized in preventing and treating atopic dermatitis with asthma.

Spatial organization of bacterial flora in normal and inflamed intestine: A fluorescence in situ hybridization study in mice

AIM: To studythe role of intestinal flora in inflammatory bowel disease (IBD).METHODS: The spatial organization of intestinal flora was investigated in normal mice and in two models of murine colitis using fluorescence in situ hybridization.RESULTS: The murine small intestine was nearly bacteriafree. The normal colonic flora was organized in three distinct compartments (crypt, interlaced, and fecal), each with different bacterial compositions. Crypt bacteria were present in the cecum and proximal colon. The fecal compartment was composed of homogeneously mixed bacterial groups that directly contacted the colonic wall in the cecum but were separated from the proximal colonic wall by a dense interlaced layer. Beginning in the middle colon, a mucus gap of growing thickness physically separated all intestinal bacteria from contact with the epithelium. Colonic inflammation was accompanied with a depletion of bacteria within the fecal compartment, a reduced surface area in which feces had direct contact with the colonic wall, increased thickness and spread of the mucus gap, and massive increases of bacterial concentrations in the crypt and interlaced compartments. Adhesive and infiltrative bacteria were observed in inflamed colon only, with dominant Bacteroides species.CONCLUSION: The proximal and distal colons are functionally different organs with respect to the intestinal flora, representing a bioreactor and a Segregation device.The highly organized structure of the colonic flora, its specific arrangement in different colonic segments, and its specialized response to inflammatory stimuli indicate that the intestinal flora is an innate part of host immunity that is under complex control.

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.

An investigation of the influence of intestinal flora in external traditional Chinese medicine therapy

External therapy,which has been used for millennia to treat disease,has now become the newest member of complementary and alternative therapies.A growing number of clinical studies and animal experiments have shown that external therapy exerts a positive effect on the intestinal flora.In this paper,we review the research related to external therapy on various systemic diseases and focus on changes in the intestinal flora.We found that studies on external therapy are dominated by acupuncture and tuina,primarily aimed at the treatment of digestive and neurological diseases.However,the deeper mechanism of regulation of the intestinal flora by external therapy has not yet been experimentally confirmed.

Research Progress in Intestinal Flora and Hepatocellular Carcinoma

Intestinal flora are involved in environmental homeostasis and the development of many diseases within the human body. The liver, as one of the most important digestive organs in human beings, communicates with the intestinal flora and their metabolites in the intestine through the biliary system, the hepatic portal system, and the corpuscular circulation, an interrelated system known as the intestinal-hepatic axis. Hepatocellular carcinoma is the most common malignant tumor of the liver and one of the leading causes of cancer-related deaths worldwide. There is increasing evidence that intestinal flora plays an important role in the evolution of hepatocellular carcinoma. Besides, intestinal flora has great potential in the treatment of liver cancer. On this basis, this paper summarizes the relevant studies on the role of intestinal flora in the development of hepatocellular carcinoma and discusses its potential value in the treatment of hepatocellular carcinoma.

Diversity of Intestinal Flora in Elderly Patients with Type 2 Diabetes Mellitus with Early Nephropathy

Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropathy group)and 51 elderly patients with type 2 diabetes mellitus(type 2 diabetes mellitus group)admitted to our hospital from January 2021 to October 2022 were retrospectively analyzed,with 39 healthy people who underwent a physical examination in our hospital during the same period as the control group.The fecal specimens of the three groups were collected,and the 16S rDNAs of bacteria in the fecal samples were extracted,amplified,and sequenced for intestinal flora operational taxonomic unit(OTU)classification and Alpha diversity analysis.Results:(1)Intestinal flora OTUs:there were 545 intestinal flora OTUs unique to the control group,424 intestinal flora OTUs unique to diabetic nephropathy,and 321 intestinal flora OTUs unique to the type 2 diabetes group.There were 403 intestinal flora OTUs common to the control group and diabetic nephropathy group,256 intestinal flora OTUs common to the control group and type 2 diabetes group,and 298 intestinal flora OTUs common to the type 2 diabetes group and diabetic nephropathy group.235 intestinal flora OTUs were common to all 3 groups of subjects.(2)Alpha diversity:The statistical analysis indicated that there was a statistically significant difference(P<0.05)in the Alpha diversity of intestinal flora,as assessed by the Ace index and Simpson’s index,among the three subject groups.However,no statistical significance(P>0.05)was observed when comparing the Chao 1 index and Shannon index.Further observation of the Ace index and Simpson index in the three groups revealed that both the diabetic nephropathy group and the type 2 diabetes mellitus group had lower values than the control group.Conclusion:The diversity of intestinal flora decreases in elderly patients with type 2 diabetes mellitus with early nephropathy.

Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

Study of Immunotherapy and Intestinal Flora Changes in Patients with Liver Cancer

Hepatocellular carcinoma (HCC) is one of the common major malignancies worldwide and has the third highest mortality rate of any malignancy. The current field of treatment for hepatocellular carcinoma is multidisciplinary in involvement and a combination of therapeutic approaches, among which immunotherapy is the treatment modality for advanced hepatocellular carcinoma. This review provides new ideas for developing immunotherapy regimens and improving the efficacy of immunotherapy for patients with advanced liver cancer by summarising the progress of intestinal flora in the immunotherapy of patients with liver cancer.

Research progress on the correlation between intestinal microflora disorder and liver disease

In recent years,the relationship between intestinal flora and liver disease has become an important research direction of liver diseases.A growing body of evidence indicates that gut bacteria play a key role in the pathophysiology of liver disease,this article combed the at home and abroad in recent years,the changes of intestinal flora and autoimmune liver disease,alcoholic liver disease,fatty liver disease related to metabolism,hepatitis b viral hepatitis,cirrhosis and liver cancer occurrence and progress of relationship of related research,And the new progress of regulating intestinal microecology in the treatment of liver diseases.Dysregulation of intestinal flora plays an important role in the occurrence and development of liver diseases.Regulating intestinal flora to improve the prognosis of liver diseases will be an important development direction in the future.

Analysis of the intestinal flora in patientswith primary liver cancer

Objective To investigate the differences in intestinal flora of patients with primary liver cancer and ofhealthy individuals and to investigate the effect of the differential flora on the development of liver cancer.Methods Overall, 67 patients with primary liver cancer who received systematic and complete treatmentbetween January 2019 and December 2020 at the Sixth People’s Hospital of Qingdao and had completeclinical data were enrolled in this study, and 26 individuals who were healthy on physical examination inthe same period were used as healthy controls. Macro genome and 16s ribosome Deoxyribo Nucleic Acid(rDNA) high-throughput sequencing were performed on the stool flora of the enrolled patients and controls,and the differences in the intestinal flora were analyzed using the LEfSe bioinformatics software.Results Compared with the control samples, all the tested patient samples showed statistically significantdifferences in the number of colonies of 5 bacterial phyla, 5 orders, 8 families, 11 genera, and 14 species(P < 0.05).Conclusion Compared with healthy people, patients with primary liver cancer have significant differencesin the intestinal flora composition. The alteration of the intestinal flora may be correlated with the occurrenceof primary liver cancer, and the intestinal flora may become a novel target for the prevention and treatmentof primary liver cancer.

Intestinal Flora and Gastrointestinal Tumors

Intestinal flora is a large and complex micro-ecosystem, and the growth and proliferation activities of different flora will have an important impact on the occurrence and development of gastric cancer and colorectal cancer as well as related treatment. This article reviews the latest research progress on the relationship between intestinal flora and gastric cancer and colorectal cancer.

Intestinal flora and depressive disorders:exploration and prospect of microbial-gut-brain axis

This paper examines the correlation between depressive disorders and intestinal flora.Depression is a common affective disorder characterized by low mood,loss of interest,anhedonia,high incidence,high recurrence rate,high disability rate,and high medical costs.The incidence and harmfulness of depressive disorder are gradually increasing,and its etiology is complex and diverse,among which the abnormal intestinal flora is considered to be one of the causes of depressive disorder.This article reviews the results of several studies that found intestinal flora imbalance in depressed patients,including changes in the type and quantity of flora and changes in metabolic pathways.In addition,antibiotic and probiotic treatments have also been shown to be effective in alleviating depressive symptoms,further indicating the importance of intestinal flora disturbances in the pathogenesis of depression.We also explored the relationship between intestinal flora and the pathogenesis of depressive disorders.Through neuro-immuno-endo-crine-metabolic pathways,intestinal flora can affect the function of the central nervous system,cause changes in the host’s mental behavior,and lead to or aggravate depressive symptoms.Overall,this study not only found differences in the intestinal flora of patients with depressive disorders but also revealed the potential role of intestinal flora in the pathogenesis.Importantly,this provides a new theoretical basis for further clarifying the pathogenesis of depressive disorders and formulating diagnosis and treatment strategies.

Research progress of traditional Chinese medicine compound in the treatment of gout based on intestinal flora

Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long history and remarkable clinical effect in treating gout patients,and has been widely used.Intestinal flora and its metabolites are the focus of current research,which can promote intestinal mucosal barrier,improve immunity and improve metabolism.The regulation of intestinal flora can reduce serum uric acid and inhibit inflammation to fight gouty arthritis.Moreover,the mechanism of intestinal flora is related to the spleen in Chinese medicine theory.Therefore,this study discusses the research mechanism and clinical application of traditional Chinese medicine compound in treating gout by regulating intestinal flora,and provides theoretical basis for the clinical application of traditional Chinese medicine and the expansion of new dosage forms.

Correlation of gut microorganisms and non-volatile flavor substances provides new insights for breeding Scylla paramamosain

The farming of Scylla paramamosain with specific flavors has a higher commercial value,and the flavors are related to the integrated farming environment and non-volatile flavor substances,while the survival environment is one of the important ways to source gut microorganisms in the organism.In this study,the levels of dominant taxa in the gut flora of S.paramamosain from Mong Cai,Vietnam(VN),Taishan City,Guangdong Province(TS)of China,and Ninghai County,Ningbo City(NB)Zhejiang Province of China converged with those of S.paramamosain from Sanmen County,Ningbo City(CK 1,CK 2,and CK 3)at 28 d of domestication.The top 15 genera with the highest abundance of VN,TS,and NB gut flora were the same as CK 1,CK 2,and CK 3,but with different percentages,and gradually converged to CK 1,CK 2,and CK 3,respectively,at 28 d of domestication.Correlation between intestinal flora and non-volatile flavor substances in the hepatopancreas at the percentage level of relative abundance of bacterial genera found that above 28 d of domestication,Muribaculaceae,Psychrilyobacter,Clostridia_vadinBB 60_group,Halarcobacter Carboxylicivirga,Sediminispirochaeta may be the most important genera affecting flavor amino acids of VN.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Psychrilyobacter,and Pseudomonas may be the most important genera affecting flavor amino acids of NB.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Vibrio,and Sphingomonas may be the most important genera affecting flavor amino acids of TS.These results show that the intestinal flora structure of crabs from different areas were domesticated in the same area for at least 28 d before they converged to that of the domesticated crab,and the most important genera affecting the flavor amino acids of TS,VN,and NB were also identified.The results of this study provide a reference and basis for the technique of directional cultivation of the flavor quality of the crab.