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.

Energy metabolism,immune function,and intestinal flora in rats with kidney-yin deficiency treated with raw or saltwater-processed Phellodendron chinense Schneid

Objective:To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid.(RPC)and saltwater-processed PC(SPC)in the treatment of rats with a kidney-yin deficiency pattern(KYDP).Methods:Healthy rats were administered hydrocortisone to establish a KYDP model.The rats were divided into seven groups:blank control,model,positive control(Liuwei Dihuang pills),high-dose RPC,low-dose RPC,high-dose SPC,and low-dose SPC.Enzyme-linked immunosorbent assay was used to measure the levels of cAMP,cGMP,TRH,TSH,T3,T4,IFN-g,TNF-a,and testosterone in the serum and the levels of Na^(+)-K^(+)-ATPase and Ca ^(2+)-Mg ^(2+)-ATPase in the liver.TRH mRNA expression in the rat hypo-thalamus was measured using RT-PCR.THRa1+2 protein expression in the hypothalamus of rats was measured using Western blot.Immunohistochemistry was performed to determine the expression levels of FAS,FasL,and TSHR.Flow cytometry was used to determine CD4^(+)and CD8^(+)T lymphocyte levels.Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats.Results:The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group(P=0.048).Compared with the model group,after administration,the levels of the above-mentioned serum and liver indexes decreased,except that of testosterone.The CD4^(+)/CD8^(+)ratio also decreased.Compared with the RPC group,the levels of T3,IFN-g,FAS,FasL,and TSHR in the SPC group decreased whereas that of testosterone increased.Additionally,immune function and intestinal flora diversity improved in the SPC group.SPC proved to be more effective in improving liver energy meta-bolism in KYDP rats than RPC.Conclusion:SPC had a better therapeutic effect on KYDP than RPC.The underlying mechanism of action may be related to improvements in liver energy metabolism,immune function,and intestinal flora diversity.

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.

The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats

BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.

Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.

Analysis of the anti-T2DM components in dichloromethane fraction of Schisandra sphenanthera and its mechanism

Background:The type 2 diabetes mellitus(T2DM)pharmacodynamic study of various parts of Schisandra sphenanthera was conducted in the previous stage,and it was found that dichloromethane extracted part(SDP)had a significant hypoglycemic effect.Therefore,the components of SDP were analyzed,and the specific mechanism of its anti-T2DM was explored.Methods:We used a high-fat,high-sugar diet in combination with streptozotocin to induce a T2DM rat model,and the model rats were divided into two groups according to body weight and blood glucose.Triglyceride,oral glucose tolerance test,fasting blood glucose,low density lipoprotein cholesterol,superoxide dismutase,insulin,glycated hemoglobin,total cholesterol,nonesterified free fatty acids,alanine aminotransferase,high-density lipoprotein cholesterol,aspartate aminotransferase,malondialdehyde,and glutathione peroxidase were measured,organ indices were calculated,and pathological sections of pancreas and liver were observed.The 16S rRNA V3–V4 region of intestinal flora was sequenced to explore the effect of SDP on biochemical indicators and intestinal flora.Based on the above indicators,the anti-T2DM mechanism of SDP in Schisandra sphenanthera was analyzed.Results:After six weeks of administration,the biochemical indices of diabetic rats were diminished compared to the control group.And SDP could significantly increase the gut microbialα-diversity index,resulting in significant changes in the flora of T2DM rats,with increased richness and diversity,reduced harmful flora,and significantly back-regulated the levels of acetic acid,propionic acid,and butyric acid.Conclusion:SDP can improve the symptoms associated with elevated blood glucose,dyslipidemia,elevated fasting insulin levels,and damaged glucose tolerance in rats.SDP against T2DM may be through the control of intestinal flora to normalize and exert anti-diabetic effect;its main active components may be lignans and terpenoids.

Effects of sepsis and its treatment measures on intestinal flora structure in critical care patients

BACKGROUND Sepsis is a common disease in intensive care units,with high morbidity and mortality.Intestinal microecology plays a vital part in the development and progression of this disease,possibly because sepsis and its treatment cause specific changes in the composition of the intestinal flora.AIM To investigate the characteristics of intestinal flora disturbance in sepsis patients treated with antibiotics.METHODS In this prospective comparative study,we enrolled ten patients with sepsis(sepsis group),hospitalized in the Department of Critical Care Medicine of the General Hospital,Ningxia Medical University,China(a class IIIa general hospital)from February 2017 to June 2017;ten patients without sepsis hospitalized in the same period(non-sepsis group)and ten healthy individuals(control group)were also enrolled.Fecal samples collected from the three groups were subjected to 16S rRNA gene sequencing and the intestinal flora diversity,structure,and composition were determined.Additionally,the dynamics of the intestinal flora diversity,structure,and composition in sepsis patients were investigated via 16S rRNA gene sequencing of samples collected 0 d,3 d,and 7 d after admittance to the intensive care unit.Correlations between the serum levels of procalcitonin,endotoxin,diamine oxidase,and D-lactic acid and the intestinal flora composition of sepsis patients were also investigated.RESULTS Compared with the healthy control group,sepsis and non-sepsis patients showed reduced intestinal floraα-diversity and a distinct flora structure,with Firmicutes as the dominant phylum,and significantly decreased proportions of Bacteroidetes,as well as Prevotella and Lachnospira,among other genera.Of note,the proportion of Enterococcus was significantly increased in the intestinal tract of sepsis patients.Interestingly,theα-diversity in the sepsis group decreased gradually,from days 1 to 7 of treatment.However,pairwise comparisons showed that both the diversity and structure of the intestinal flora were not significantly different considering the three different time points studied.Curiously,the serum levels of procalcitonin,endotoxin,diamine oxidase,and D-lactic acid in sepsis patients correlated with the prevalence of various bacterial genera.For example,the prevalence of Ruminococcus was positively correlated with serum procalcitonin,endotoxins,and diamine oxidase;similarly,the prevalence of Roseburia was positively correlated with serum procalcitonin,endotoxins,and D-lactic acid.CONCLUSION Sepsis patients in intensive care units show dysbiosis,lasting for at least 1 wk.

Using 16S rDNA Sequencing Technology to Preliminarily Analyze Intestinal Flora in Children with Mycoplasma pneumoniae Pneumonia

Objective We investigated changes in the intestinal flora of children with Mycoplasma pneumoniae pneumonia(MPP).Methods Between September 2019 and November 2019,stool samples from 14 children with MPP from The Fourth Hospital of Baotou city,Inner Mongolia Autonomous Region,were collected and divided into general treatment(AF)and probiotic(AFY)groups,according to the treatment of“combined Bifidobacterium,Lactobacillus,Enterococcus,and Bacillus cereus tablets live”.Highthroughput 16S rDNA sequencing was used to identify intestinal flora.Results Intestinal flora abundance and diversity in children with MPP were decreased.Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls(P<.05).When compared with healthy controls,the proportion of Enterorhabdus was lower in the AF group,while the proportion of Lachnoclostridium was higher(P<0.05).The proportion of Bifidobacteria and Akkermansia was lower in the AFY group but Enterococcus,Lachnoclostridium,Roseburia,and Erysipelatoclostridium proportions were higher.The proportion of Escherichia coli-Shigella in the AFY group after treatment was decreased(P<0.05).Conclusions The intestinal flora of children with MPP is disturbed,manifested as decreased abundance and diversity,and decreased Bifidobacteria.Our probiotic mixture partly improved intestinal flora disorders.

Moxibustion inhibits interleukin-12 and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis

AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response.

Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value

Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic cholestasis,a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis.Gut microbes,consisting of microorganisms colonized in the human gut,play an important role in nutrient intake,metabolic homeostasis,immune regulation,and immune regulation;however,their presence might aid PSC development.Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC.Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria.Dysbiosis of the intestinal flora leads to increased intestinal permeability,homing of intestinal lymphocytes,entry of bacteria and their associated metabolites,such as bile acids,into the liver,stimulation of hepatic immune activation,and promotion of PSC.Currently,PSC effective treatment is lacking.However,a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases(alcoholic liver disease,metabolic fatty liver,cirrhosis,and autoimmune liver disease).In addition,antibiotics,fecal microbiota transplantation,and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis,suggesting their effectiveness for PSC treatment.Therefore,this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.

New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease

Intestinal flora plays a key role in nutrient absorption,metabolism and immune defense,and is considered to be the cornerstone of maintaining the health of human hosts.Bile acids synthesized in the liver can not only promote the absorption of fat-soluble substances in the intestine,but also directly or indirectly affect the structure and function of intestinal flora.Under the action of intestinal flora,bile acids can be converted into secondary bile acids,which can be reabsorbed back to the liver through the enterohepatic circulation.The complex dialogue mechanism between intestinal flora and bile acids is involved in the development of intestinal inflammation such as inflammatory bowel disease(IBD).In this review,the effects of intestinal flora,bile acids and their interactions on IBD and the progress of treatment were reviewed.

GPP(composition of Ganoderma lucidum polysaccharides and Polyporus umbellatus polysaccharides) protects against DSS-induced murine colitis by enhancing immune function and regulating intestinal flora

Previous study have demonstrated that a compound composed of water-soluable Ganoderma lucidum polysaccharides(GLP)and Polyporus umbellatus polysaccharides(PUP)in a ratio of 3:1 named GPP enhances innate immune function in mice through enhancing the function of macrophage cells and activity of natural killer(NK)cells.Here in our research,we further investigated the effect of GPP on the diversity and composition of intestinal flora,and explored its effect on colitis model mice.The immunoregulatory verification experiments of GPP were conducted in both normal and DSS-induced mice model.Our research showed that GPP increased the diversity of intestinal microorganisms in mice with the extension of administration time.Daily GPP intake attenuated DSS-induced colon injury,protected the splenic lymphocyte proliferation ability,enhanced the serum hemolysin synthesis,and increased peripheral phagocytes and NK cell activity in model mice.Comparisons of the predominant gene pathways of the bacterial microbiota showed that DNA repair and recombination,base mismatch repair pathways was stronger in GPP-treatment group than in control group,indicating the possible molecular mechanisms of immune function regulation.Our study showed that GPP regulated immune function in both health and colitis model,and had a positive effect on maintaining intestinal flora homeostasis.

Different dietary starch patterns in lowprotein diets:effect on nitrogen efficiency,nutrient metabolism,and intestinal flora in growing pigs

Background:Protein releases amino acids faster than starch releases glucose in digestive tract of pigs fed lowprotein(LP)diets.Poor synchronization of dietary glucose and amino acids supply leads to compromised nitrogen efficiency.Dietary starch patterns modulation may improve this situation.Methods:Growing barrows(29.7±2.0 kg)were randomly allotted into 5 dietary treatments with LP diets consisting of different purified starches.Treatments included:waxy corn starch(W LP),corn starch+waxy corn starch(C+W LP),corn starch(C LP),pea starch+waxy corn starch(P+W LP)and pea starch(P LP).In the experiment,growth performance,protein deposition,nutrient metabolism,and fecal microbial community of pigs were investigated.In vitro starch digestion was used for predicting the in vivo glucose response.Results:Dietary starch in vitro glucose release profile was determined by starch source and the ratio of amylopectin and amylose.C+W LP treatment showed decreased total nitrogen excretion and plasma citrulline concentration and improved plasma leptin concentration among treatments(P<0.05).Besides,the highest nitrogen apparent biological value,whole-body protein deposition and growth performance and lowest urinary nitrogen excretion were also observed in C+W LP treatment.Compared with the other groups,C+W LP and C LP showed increased plasma pyruvate,IGF-1,and lipase concentrations(P<0.05).The W LP group presented dramatically increased plasma alanine and urea nitrogen concentration and decreased aldolase and leptin concentrations(P<0.05).Dietary starch patterns did not make an impact on bacterial richness and diversity,but changed the taxonomic and functional structures of the microbial communities.Microbial protein fermentation product(isobutyrate and isovalerate)presented increased in P LP treatments compared with the other treatments(P<0.05).Conclusions:Dietary starch patterns modulation can regulate dietary glucose release profile,nutrient metabolism,protein turnover,and fecal microbial fermentation in pigs.The optimal dietary glucose release profile effectively strengthened whole-body protein deposition and improve nitrogen efficiency and growth performance in growing pigs fed LP diets.

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.