Composition Of Intestinal Flora Research Articles

Probiotics: functional food ingredients with the potential to reduce hypertension.

Hypertension is an increasingly pressing public health concern across the globe. It can be triggered by a variety of factors such as age and diet, as well as the stress of modern life. The traditional treatment of hypertension includes calcium ion blockers, angiotensin II receptor inhibitors and β-receptor blockers, but these drugs have at least some side effects. Recent studies have revealed that intestinal flora plays a vital role in maintaining and promoting human health. This is due to the type and amount of probiotics present in the flora. Probiotics can reduce hypertension symptoms through four mechanisms: regulating vascular oxidative stress, producing short-chain fatty acids, restoring endothelial cell function, and reducing inflammation. It has been reported that certain functional foods, using probiotics as their raw material, can modify the composition of intestinal flora, thus regulating hypertension symptoms. Consequently, utilizing the probiotic function of probiotics in conjunction with the properties of functional foods to treat hypertension is a novel, side-effect-free treatment method. This study seeks to summarize the various factors that contribute to hypertension, the mechanism of probiotics in mitigating hypertension, and the fermented functional foods with probiotic strains, in order to provide a basis for the development of functional foods which utilize probiotics as their raw material and may have the potential to reduce hypertension.

Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet

ObjectivesBuckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats. MethodsHere, using a high-fat diet–induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively. ResultsOur results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis. ConclusionsA QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.

Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats

To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.

Hypoglycemic effect of polysaccharides of Dendrobium officinale compound on type 2 diabetic mice

This study investigated the hypoglycemic effect of polysaccharides of Dendrobium officinale compound (DOCP) on streptozotocin induced type 2 diabetic mice. Compared with the model group, the fasting blood glucose value of DOCP (800 mg/kg) at day 35 of the study significantly decreased (P < 0.05). Meanwhile, DOCP (800 mg/kg) significantly increased the serum insulin content and reduced the insulin resistance in type 2 diabetic mice. Furthermore, DOCP reduced the serum total cholesterol, triglyceride and LDL-C concentrations, increased the antioxidant capability, and improved liver and pancreas damage in type 2 diabetic mice. DOCP increased the diversity of intestinal flora composition, and the abundance of beneficial bacteria such as Lactobacillus and Bifidobacteriaceae. DOCP (800 mg/kg) induced up-regulation expression of genes such as Glut2, Gck, Pklr, Insr, Pdx-1 and Ins1, but elicited down-regulation of Caspase-3. These results indicate that DOCP achieves antidiabetic and hypolipidemic effects in type 2 diabetic mice.

Ginsenoside Rh4 Improves Hepatic Lipid Metabolism and Inflammation in a Model of NAFLD by Targeting the Gut Liver Axis and Modulating the FXR Signaling Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a series of disorders of liver metabolism caused by the accumulation of lipids in the liver, which is considered the main cause of hepatocellular carcinoma. Our previous study demonstrated the promising efficacy of ginsenoside Rh4 in improving the intestinal tract and its related metabolites. Meanwhile, many studies in the literature have investigated the gut microbiota and its metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), which play a key role in the pathogenesis of NAFLD. Therefore, this study focused on whether Rh4 could achieve therapeutic effects on NAFLD through the gut-liver axis. The results showed that Rh4 exhibited sound therapeutic effects on the NAFLD model induced by the Western diet and CCl4 in mice. In the liver, the degrees of hepatic steatosis, lobular inflammation levels, and bile acid in the liver tissue were improved after Rh4 treatment. At the same time, Rh4 treatment significantly increased the levels of intestinal SCFAs and BAs, and these changes were accompanied by the complementary diversity and composition of intestinal flora. In addition, correlation analysis showed that Rh4 affected the expression of proteins involved in the farnesoid X receptor (FXR) signaling pathway in the liver and intestine, which modulates hepatic lipid metabolism, inflammation, and proteins related to bile acid regulation. In conclusion, our study provides a valuable insight into how Rh4 targets the gut-liver axis for the development of NAFLD, which indicates that Rh4 may be a promising candidate for the clinical therapy of NAFLD.

Assessments of the effects of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) on human intestinal health from the aspects of intestinal flora changes and cytotoxicity to human cells

Organophosphorus flame retardants (OPFRs) are now drawing the public's attention due to their potential toxicity. Given that contaminated food may result in the ingestion of OPFRs to the human intestine, further investigation is required to determine the potential adverse effects of these compounds on human intestinal health. The present study aimed to comprehensively assess the effect of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a typical OPFR, on human intestinal health by evaluating both intestinal flora and human cell Caco-2. Based on the results, TDCPP exposure altered the composition of intestinal flora and increased the proportion of pathogenic bacteria. PICRUSt2 analysis revealed that certain pathways were affected by TDCPP, and the resulting metabolic disorders might cause health problems. Orthologous genes of glutathione S-transferase and multidrug efflux system were up-regulated, demonstrating that the bacteria resisted TDCPP to maintain their vitality. Compared to the other two OPFRs, TDCPP induced greater cytotoxicity, and the results were consistent with the dose-effect relationship. Three OPFRs, especially TDCPP, caused the release of lactate dehydrogenase, accumulation of ROS, decline in mitochondrial membrane potential and increase in intracellular Ca2+, which could consequently induce cell death. The simultaneous effects of TDCPP on both intestinal cells and intestinal flora are likely to engender more severe intestinal health issues.

Cinnamon oil solid self-microemulsion mediates chronic mild stress-induced depression in mice by modulating monoamine neurotransmitters, corticosterone, inflammation cytokines, and intestinal flora

Cinnamon oil (CO) is a classic Chinese medicine with excellent soothing effects on exhaustion, weakness and depression. Cinnamaldehyde is the main active ingredient of cinnamic oil. Although CO have antidepression-like effects, limited information is available. Furthermore, the disadvantages of CO, such as low oral availability and difficult portability, limit its development. In this study, a Cinnamon Oil Solid Self-Microemulsifying Drug Delivery System (CO-S-SME) was designed, prepared. In addition, we explored the effects and mechanisms of CO-S-SME on chronic unpredictable mild stress (CUMS)-induced depression-like behavior, monoamine neurotransmitters, inflammatory factors, intestinal flora in mice. Mice were subjected CUMS to establish the depression model. The antidepressant effect of CO-S-SME was evaluated by behavioral tests. In addition, the expression levels of neurotransmitters, corticosterone (CORT) and inflammatory factors in CUMS mice were analyzed by enzyme-linked immunosorbent assay. In addition, we explored the effects of CO-S-SME on the diversity and richness of intestinal flora of mice in each group. Behavioral tests showed that CO-S-SME could effectively improve depression-like behaviors in CUMS mice. Specifically, CO-S-SME treatment effectively increased neurotransmitter levels and reduced the expressions of corticosterone and inflammatory factors in CUMS mice. CO-S-SME also changed the intestinal flora composition, decreased the ratio of Firmicutes to Bacteroidetes, reduced relative abundances of Lactobacillus, modulated Alpha diversity and beta diversity. These results suggest that CO-S-SME an act as a good antidepressant, exhibiting effects via monoamine neurotransmitters, CORT, inflammation cytokines, and intestinal flora.

Metagenomics study on taxonomic and functional change of gut microbiota in patients with obesity with PCOS treated with exenatide combination with metformin or metformin alone

Objective To investigate the effect of exenatide treatment on the composition of intestinal flora and metabolic pathways in patients with obesity with polycystic ovary syndrome. Methods Patients with obesity with polycystic ovary syndrome (PCOS) were distributed to two groups: one received exenatide combined with metformin (COM group, n = 14) and the other used metformin alone (MF group, n = 15). Fresh fecal specimens from the participants, including 29 patients with obesity with PCOS and 6 healthy controls, were collected for metagenomic sequencing. The effect of exenatide combination with metformin or metformin alone on the composition and function of intestinal flora in patients with obesity with PCOS were compared by bioinformatics analysis. Results The level of BMI, TT, HbA1c, and HDL-c was significantly improved in both groups. The MF and COM groups were abundant in Firmicutes, Bacteroidetes, Uroviricota, Actinobacteria, and Proteobacteria. Abundance of Bacteroidetes, Proteobacteria, Hungatella, and certain probiotics like Phocaeicola and Anaerobutyricum significantly increased in both groups after treatment. Enriched microbial species in the MF and COM group were different. Clostridium, Fusobacterium, and Oxalobacter were the main bacteria in the post-MF group, while Lactococcus_garvieae, Clostridium_perfringens, and Coprococcus_sp_AF16_5 were the main bacteria in the post-COM group. The post-COM group had more probiotic species including Bifidobacterium, Prevotella, and Anaerobutyricum after treatment. Conclusion Both exenatide combined with metformin and metformin monotherapy can improve metabolic and endocrine markers, and the diversity and abundance of gut microbiota in patients with obesity with PCOS. The effects of the combination and monotherapy agents on intestinal flora were consistent to some extent but also unique respectively.

Amplicon-based metagenomic association analysis of gut microbiota in relation to egg-laying period and breeds of hens

BackgroundThe gut microbiota plays an essential role in maintaining gut homeostasis and improving performance, with the composition of microbial communities visibly differing across different laying stages in hens and significantly correlating with egg production. To gain further insights into the association between microbial community characteristics and laying periods in Hy-Line variety brown and Isa brown laying hens, we conducted a 16S rRNA amplicon sequencing survey.ResultsOur result revealed the diversity of bacteria in the early laying period was commonly higher than peak, and in Hy-Line variety brown laying hens were generally higher than Isa brown. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the structure and composition of the gut microbiota of laying hens exhibited significant differences among different groups. Phylum Firmicutes, Bacteroidota, Proteobacteria, and Fusobacteriota were found that dominant in the host’s feces. Therein, the abundance of Fusobacteriota was higher in the peak period than in the early period, while the abundance of Cyanobacteria in the early period was higher in two breeds of hens. Furthermore, random forest based on machine learning showed that there were several distinctly abundant genera, which can be used as potential biomarkers to differentiate the different groups of laying periods and breeds. In addition, the prediction of biological function indicated the existing discrepancy in microbial function among the microbiota of four groups.ConclusionsOur findings offer new insights into the bacterial diversity and intestinal flora composition of different strains of laying hens during various laying periods, contributing significantly to the improvement of production performance and the prevention of chicken diseases.

Adherent-invasive Escherichia coli LF82 aggravated intestinal inflammation in colitis mice by affecting the gut microbiota and Th17/Treg cell differentiation balance.

The imbalance of Th17 and Treg cell differentiation, intestinal flora imbalance, and intestinal mucosal barrier damage may be important links in the occurrence and development of inflammatory bowel disease (IBD) since Th17 and Treg differentiation are affected by the intestinal flora. This study aimed to explore the effect of Escherichia coli (E. coli) LF82 on the differentiation of Th17 and Treg cells and the role of the intestinal flora in mouse colitis. The effects of E. coli LF82 infection on intestinal inflammation were evaluated by analyzing the disease activity index, histology, myeloperoxidase activity, FITC-D fluorescence value, and claudin-1 and ZO-1 expression. The effects of E. coli LF82 on the Th17/Treg balance and intestinal flora were analyzed by flow cytometry and 16S rDNA sequencing. Inflammatory markers, changes in the intestinal flora, and Th17/Treg cells were then detected after transplanting fecal bacteria from normal mice into colitis mice infected by E. coli LF82. We found that E. coli LF82 infection can aggravate the intestinal inflammation of mice colitis, destroy their intestinal mucosal barrier, increase intestinal mucosal permeability, and aggravate the imbalance of Th17/Treg differentiation and the disorder of intestinal flora. After improving the intestinal flora imbalance by fecal bacteria transplantation, intestinal inflammation and intestinal mucosal barrier damage were reduced, and the differentiation balance of Th17 and Treg cells was restored. This study showed that E. coli LF82 infection aggravates intestinal inflammation and intestinal mucosal barrier damage in colitis by affecting the intestinal flora composition and indirectly regulating the Th17 and Treg cell differentiation balance.

Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1.

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan'an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

Effects of the synbiotic composed of mangiferin and Lactobacillus reuteri 1-12 on type 2 diabetes mellitus rats.

Many synbiotics are effective for the prevention and treatment of type 2 diabetes mellitus (T2DM). In the treatment of T2DM, synbiotics often regulate the composition of intestinal flora, which autoinducer-2 (AI-2) may play an important role. Whether the changes of intestinal flora are related to AI-2 during synbiotics treatment of T2DM is a topic worth studying. We elucidated the effects of synbiotic composed of mangiferin and Lactobacillus reuteri 1-12 (SML) on T2DM rats. Male Spraque-Dawley rats were injected intraperitoneally with streptozotocin (STZ) and randomly grouped. After that, biochemical parameters, intestinal flora, fecal AI-2, and intestinal colonization of L. reuteri were detected. The results showed that SML had a hypoglycemic effect and mitigated the organ lesions of the liver and pancreas. Also, SML regulated biochemical parameters such as short chain fatty acids (SCFAs), lipopolysaccharides (LPS), intercellular cell adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). On the other hand, the proportion of probiotics, such as Lactobacillus acidophilus, L. reuteri, Bifidobacterium pseudolongum, Lactobacillus murinus, and Lactobacillus johnsonii, were elevated by the treatment of SML. In addition, SML promoted the colonization and proliferation of L. reuteri in the gut. Another thing to consider was that AI-2 was positively correlated with the total number of OTUs sequences and SML boosted AI-2 in the gut. Taken together, these results supported that SML may modulate intestinal flora through AI-2 to treat T2DM. This study provided a novel alternative strategy for the treatment of T2DM in future.

Effects of Simulated In Vitro Digestion on the Structural Characteristics, Inhibitory Activity on α-Glucosidase, and Fermentation Behaviours of a Polysaccharide from Anemarrhena asphodeloides Bunge.

The purpose of this study is to investigate the effects of the simulated saliva-gastrointestinal digestion of AABP-2B on its structural features, inhibitory α-glucosidase activity, and human gut microbiota. The salivary-gastrointestinal digestion results show that there is no significant change in the molecular weight of AABP-2B, and no free monosaccharides are released. This indicates that, under a simulated digestive condition, AABP-2B is not degraded and can be further utilized by gut microbiota. AABP-2B still possessed good inhibitory activity on α-glucosidase after salivary-gastrointestinal digestion, which may be attributed to the largely unchanged structural characteristics of AABP-2B after simulated digestion. Furthermore, in vitro fecal fermentation with AABP-2B after salivary-gastrointestinal digestion showed that AABP-2B modulated the gut microbiota structure and increased the relative proportions of Prevotella, Faecalibacterium, and Megasphaera. AABP-2B can also modify the intestinal flora composition by inhibiting pathogen growth. Moreover, the AABP-2B group resulted in a significant increase in short-chain fatty acid (SCFAs) content during fermentation. These findings demonstrate that AABP-2B can be used as a prebiotic or functional food to promote gut health.

Studies on nutritional intervention of ginkgo starch-lauric acid complex in obese rats induced by a high-fat diet

Ginkgo starch was frequently used in food, but consuming too much of it could increase postprandial blood sugar and potentially cause obesity. Through molecular docking, we discovered that lauric acid enters the spiral cavity formed by amylose molecules to form a stable compound. The compound exhibited a V-type structure, enhanced relative crystallinity, short-range order, and long-range order, while also experiencing a 20% reduction in in vitro digestibility. The complex may also lessen body weight, serum triglyceride (TG) and total cholesterol (TC) levels in rats, as well as improve hepatic fat accumulation and intestinal flora composition. It's interesting to note that the complex greatly boosted the number of good bacteria in rats, and that these bacteria positively connected with the production of short-chain fatty acids (SCFAS), superoxide dismutase (SOD), TC, and TG. In conclusion, the high-fat diet-induced obesity is significantly improved by the ginkgo starch-lauric acid combination (GSL).

Changes of Intestinal Flora in Patients with Atrial Fibrillation and Its Correlation with Cardiovascular Risk Factors.

Based on the 16S rDNA sequence, intestinal flora changes in atrial fibrillation (AF) patients were monitored, the correlation between the changes and - score was analyzed, and the possible related factors affecting the changes of intestinal flora were investigated. According to the inclusion criteria, 53 AF patients were selected as atrial fibrillation group (Group AF), detection of C-reactive protein (CRP), homocysteine (Hcy), total bile acid (TBA), brain natriuretic peptide (BNP), High-sensitivity cardiac troponin (Hs-cTn) and left ventricular ejection fraction (LVEF) were accomplished. A total of 29 healthy subjects who underwent physical examination with matched gender and age were selected as the healthy group (Group H), and the same examinations as in Group AF were handled. Structural composition of intestinal flora was detected and analyzed by 16S rRNA sequencing technology. Flora differences between Group AF and Group H were counted, and the correlation analysis among age, Hs-cTn, CRP, TBA, Hcy, BNP and LVEF were explored. Meanwhile, - score of 53 AF patients was fulfilled, then patients were divided into three subgroups according to different scores, namely: 0 point (AF-0, n = 9), 1 point (AF-1, n = 15), 2 points (AF-2, n = 29). Finally, the correlation of intestinal flora differences and - scores were analyzed. In terms of Alpha diversity, compared with the control group, the abundance and diversity of flora in Group AF were observably reduced. However, at phylum and class level, there was no notable difference in community structure between Group AF and Group H (p 0.05). Further statistics revealed that the composition and abundance of intestinal flora in Group AF were prominently different from those in Group H at phylum, class, order and family levels, which were correlated with CRP and LVEF. Additionally, bioinformatics analysis comparison was performed on three - score subgroups of Group AF with Group H. It was reported that at phylum level, the relative abundance of Firmicutes in Group AF-2 and Chloroflexi in Group H was higher. At class level, the relative abundance of Sphingobacteriia, Flavobacteriia and Alphaproteobacteria was higher in group H. At order level, the relative abundance of Sphingobacteriales, Micrococcales, Flavobacteriales, Sphingobacteriales and Rhizobiales in group H was higher. At family level, the relative abundance of Sphingobacteriaceae, Flavobacteriaceae and Clostridiaceae in group H was higher. At genus level, the relative abundance of Sphingobacterium in group H, Clostridiumsensustricto-1 in Group AF-2, Dialister and Allisonella in Group AF-1, and Prevotella-9 in Group AF-0 were higher. There were changes in the relative abundance of intestinal flora at phylum, class, order and family levels, which was concerned with LVEF and CRP value, whereas Alpha diversity index of the flora decreased. The composition and relative abundance of intestinal flora varied in AF patients with - scores of 0, 1, and 2.

How to Choose a Treatment for Immune Checkpoint Inhibitor-associated Colitis: Biologics, or Fecal Microbial Transplantation.

To the Editors, In recent years, immune checkpoint inhibitors (ICIs) have been used in an increasing number of oncology patients. Patients may experience treatment-related toxic reactions after the application of such drugs. We focus on immune-related adverse events (irAEs) caused by ICIs, of which ICI-associated colitis (ICIAC) is one of the most common toxic reactions in ICIs therapy. Immune checkpoint inhibitor–associated colitis is usually treated with steroid hormones of choice, and severe cases require combined immunosuppressive therapy. Here, we will discuss this type of colitis in terms of treatment. The management of ICIAC is based on the principles of timely and effective symptom control and reduction of recurrence and complications, thus achieving the maximum benefit of antineoplastic therapy. First, treatment is preferred to steroids, which are effective in most patients. The recommended first-line treatment for grade 3/4 immune-associated small bowel colitis (irEC) is high-dose glucocorticoids, but some patients with colitis become steroid-refractory.1Second, immunosuppressive therapy is used, often with infliximab (IFX) or vedolizumab. Abu-Sbeih et al suggested for irEC, early introduction of IFX therapy can reduce hormone dependence and lower the risk of irEC relapse compared with the risk of waiting for steroid hormone therapy to fail before using IFX.2 Third, fecal microbial transplantation (FMT) improves the intestinal flora of patients by extracting flora from donor stool samples and transferring them to patients. Fecal microbial transplantation is also increasingly used; Wang et al reported 2 cases of refractory-associated colitis patients who were successfully treated with FMT.3 In the first study, both patients showed complete clinical remission after treatment with FMT; and the other study reported the successful use of FMT to treat a patient with severe ICI-induced colitis who did not respond to steroid and infliximab treatment.4 Although this study showed to some extent that FMT was effective in patients who did not respond with infliximab, more evidence-based medical data is needed for the safety and long-term efficacy of FMT. In the future, we can combine with macrogenomic technology to detect the composition of intestinal flora and promote the application and development of fecal transplantation technology.

Research Progress of Polyphenols in the Prevention and Treatment of AD by Regulating Intestinal Flora

The human gut microbiota is known as the "second brain". Intestinal flora is a large number of microorganisms in the human gut, which is a highly diverse bacterial homeostasis system. If this homeostasis is out of balance, the intestinal flora will be disturbed, which will affect the physical health. A growing body of research has shown that intestinal flora participates in two-way communication between gut and brain through gut-brain axis (GBA) and is strongly associated with Alzheimer's disease (AD). At present, there is still a lack of effective treatment for AD. Recent studies have shown that polyphenols play a neuroprotective role by exerting their anti-inflammatory and antioxidant effects. This topic refers to a large number of recent literatures in the same field and makes a comprehensive review of them. It was found that polyphenols with complex structure could not be directly digested and absorbed by human organism, and their bioavailability was low, which affected the effective play of their health effects. The secretory enzymes in the intestinal flora convert them into small molecular metabolites that are biologically active and easy for the body to absorb. At the same time, polyphenols can the composition and function of intestinal flora by acting on its growth or metabolism, and further act on immune, endocrine and intestinal neural pathways in GBA, forming a complex network of relationships. By exerting its neuroprotective effect, it is expected to achieve the purpose of preventing and treating AD.

Multi-omics reveals Dengzhan Shengmai formulation ameliorates cognitive impairments in D-galactose-induced aging mouse model by regulating CXCL12/CXCR4 and gut microbiota.

Dengzhan Shengmai (DZSM), a traditional Chinese medicine formulation, has been administered extensively to elderly individuals with cognitive impairment (CI). However, the underlying mechanisms by which Dengzhan Shengmai improves cognitive impairment remains unknown. This study aimed to elucidate the underlying mechanism of the effect of Dengzhan Shengmai on aging-associated cognitive impairment via a comprehensive combination of transcriptomics and microbiota assessment. Dengzhan Shengmai was orally administered to a D-galactose-induced aging mouse model, and evaluation with an open field task (OFT), Morris water maze (MWM), and histopathological staining was performed. Transcriptomics and 16S rDNA sequencing were applied to elucidate the mechanism of Dengzhan Shengmai in alleviating cognitive deficits, and enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (PCR), and immunofluorescence were employed to verify the results. The results first confirmed the therapeutic effects of Dengzhan Shengmai against cognitive defects; specifically, Dengzhan Shengmai improved learning and impairment, suppressed neuro loss, and increased Nissl body morphology repair. Comprehensive integrated transcriptomics and microbiota analysis indicated that chemokine CXC motif receptor 4 (CXCR4) and its ligand CXC chemokine ligand 12 (CXCL12) were targets for improving cognitive impairments with Dengzhan Shengmai and also indirectly suppressed the intestinal flora composition. Furthermore, in vivo results confirmed that Dengzhan Shengmai suppressed the expression of CXC motif receptor 4, CXC chemokine ligand 12, and inflammatory cytokines. This suggested that Dengzhan Shengmai inhibited CXC chemokine ligand 12/CXC motif receptor 4 expression and modulated intestinal microbiome composition by influencing inflammatory factors. Thus, Dengzhan Shengmai improves aging-related cognitive impairment effects via decreased CXC chemokine ligand 12/CXC motif receptor 4 and inflammatory factor modulation to improve gut microbiota composition.

Exploring the Dose–Effect Relationship of Bifidobacterium longum in Relieving Loperamide Hydrochloride-Induced Constipation in Rats through Colon-Released Capsules

Constipation is a common disease affecting humans. Bifidobacterium longum is reportedly effective in relieving constipation. Current studies generally focus on the dose-response relationship of oral doses; however, the dose-effect relationship of B. longum in the colon, which is the primary site where B. longum exerts constipation-relieving effects, to treat constipation has not been studied. Herein, three strains of B. longum (FGSZY6M4, FJSWXJ10M2, and FSDJN6M3) were packaged in colon-released capsules to explore the dose-effect relationship in the colon. For each strain, three groups of capsules (104, 106, and 108 CFU/capsule, respectively) and one group of free probiotics (108 CFU/mL) were used to explore the colonic dose effect of B. longum. The results showed that the three strains of B. longum improved fecal water content and promoted intestinal motility by regulating gastrointestinal peptide (MTL, GAS, and VIP), aquaporin-3, and 5-hydroxytryptamine levels while promoting gastrointestinal motility and relieving constipation by regulating the intestinal flora composition of constipated rats and changing their metabolite content (short-chain fatty acids). Among the three free bacterial solution groups (108 CFU/mL), FGSZY6M4 was the most effective in relieving constipation caused by loperamide hydrochloride in rats. The optimal effective dose of each strain was 6M4 (104 CFU/day), 10M2 (106 CFU/day), and S3 (108 CFU/day) of the colon-released capsules. Therefore, for some effective strains, the dose of oral probiotics can be reduced by colon-released capsules, and constipation can be relieved without administering a great number of bacterial solutions. Therefore, investigating the most effective dose of B. longum at the colon site can help to improve the efficiency of relieving constipation.

Alterations in gut microbiota and urine metabolomics in infants with yin-deficiency constitution aged 0–2 years

BackgroundBased on the constitution theroy, infants are classified into balanced constitution (BC) and unbalanced constitution. Yin-deficiency constitution (YINDC) is a common type of unbalanced constitutions in Chinese infants. An infant's gut microbiota directly affects the child's health and has long-term effects on the maturation of the immune and endocrine systems throughout life. However, the gut microbiota of infants with YINDC remains unknown. Herein, we aimed to evaluate the intestinal flora profiles and urinary metabolites in infant with YINDC, find biomarkers to identify YINDC, and promote our understanding of infant constitution classification. MethodsConstitutional Medicine Questionnaires were used to assess the infants’ constitution types. 47 infants with 21 cases of YINDC and 26 cases of BC were included, and a cross-sectional sampling of stool and urine was conducted. Fecal microbiota was characterized using 16S rRNA sequencing, and urinary metabolomics was profiled using UPLC-Q-TOF/MS method. YINDC markers with high accuracy were identified using receiver operating characteristic (ROC) analysis. ResultsThe diversity and composition of intestinal flora and urinary metabolites differed significantly between the YINDC and BC groups. A total of 13 obviously different genera and 55 altered metabolites were identified. Stool microbiome shifts were associated with urine metabolite changes. A combined marker comprising two genera may have a high potential to identify YINDC with an AUC of 0.845. ConclusionsInfants with YINDC had a unique gut microbiota and metabolomic profile resulting in a constitutional microclassification. The altered gut microbiome in YINDC may account for the higher risk of cardiovascular diseases. Metabolomic analysis of urine showed that metabolic pathways, including histidine metabolism, proximal tubule bicarbonate reclamation, arginine biosynthesis, and steroid hormone biosynthesis, were altered in infants with YINDC. Additionally, the combined bacterial biomarker had the ability to identify YINDC. Identifying YINDC in infancy and intervening at an early stage is crucial for preventing cardiovascular diseases.