Regulatory effect of gut microbes on blood pressure

Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases.Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans.In this review,we outline the interaction between gut microbiota and hypertension,including gut microbial changes in hypertension,the effect of microbial dysbiosis on blood pressure(BP),indicators of gut microbial dysbiosis in hypertension,and the microbial genera that affect BP at the taxonomic level.For example,increases in Lactobacillus,Roseburia,Coprococcus,Akkermansia,and Bifidobacterium are associated with reduced BP,while increases in Streptococcus,Blautia,and Prevotella are associated with elevated BP.Furthermore,we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension.Finally,we summarize the commonly used treatments of hypertension that are based on gut microbes,including fecal microbiota transfer,probiotics and prebiotics,antibiotics,and dietary supplements.This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.

The human-derived novel gut commensal Luoshenia tenuis regulates body weight and food intake in mice

Many studies have revealed that gut microbes modulate host metabolism.In this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic disorders.First,by in silico analysis,we demonstrated that the L.tenuis was prevalent in the gut microbiomes of healthy humans but were depleted specifically in obesity cohorts.Further in vitro cultivation revealed that L.tenuis produced short chain fatty acids that were verified to modulate host metabolism and some other volatile metabolites to benefit hosts by anti-inflammation and anti-tumor.Second,gavage of the L.tenuis significantly decreased the body weight gain and food intake of high-fat diet-feeding C57BL/6J mice,which was in parallel with the changed expression level of genes related to satiety and feeding behavior.We then performed the gavage trial using diet induced obese mice,and it revealed that the administration of L.tenuis alleviated significantly the abnormal glucose and lipid metabolisms and reduced the inflammatory response.In summary,this study revealed a previously-unknown human gut commensal microbe that benefited host metabolism,and set the stage for the development of novel next-generation probiotic applicable for treatment of obesity and related metabolic disorders.

Modulation of Gut Microbiota in Pathological States

The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.

Bile acids and microbes in metabolic disease

Bile acids(BAs)serve as physiological detergents that enable the intestinal absorption and transportation of nutrients,lipids and vitamins.BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism,microbiota habitat regulation and cell signaling.BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy,lipid,glucose,and drug metabolism.The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism.Therefore,altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes,such as diabetes mellitus,obesity/hypercholesterolemia,and cardiovascular diseases.BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases.This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases.Moreover,we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders.Finally,we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.

Clinical Report on the Treatment of Post-stroke Cognitive Impairment Based on Microbe-Gut-Brain Axis Theory

Based on the close relationship between MGBA and PSCI,one PSCI related case is reported,and it is emphasized to improve clinicians'understanding of MGBA theory in the treatment of PSCI,thereby providing new ideas for exploring pathogenesis and treatment of PSCI.

2023:A year of accomplishments for the 13 Science Citation Index Expanded-and Emerging Sources Citation Index-indexed Baishideng journals

In 2023,Baishideng Publishing Group(Baishideng)routinely published 47 openaccess journals,including 46 English-language journals and 1 Chinese-language journal.Our successes were accomplished through the collective dedicated efforts of Baishideng staffs,Editorial Board Members,and Peer Reviewers.Among these 47 Baishideng journals,7 are included in the Science Citation Index Expanded(SCIE)and 6 in the Emerging Sources Citation Index(ESCI).With the support of Baishideng authors,company staffs,Editorial Board Members,and Peer Reviewers,the publication work of 2023 is about to be successfully completed.This editorial summarizes the 2023 activities and accomplishments of the 13 SCIEand ESCI-indexed Baishideng journals,outlines the Baishideng publishing policy changes and additions made this year,and highlights the unique advantages of Baishideng journals.

Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles

Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

A review on anti-inflammation activity of phenol compound paeonol

Paeonol is a bioactive phenol present in Dioscorea japonica,Paeonia suff ruticosa and Paeonia lactiflora.It is the main active ingredient in the traditional Chinese medicines Mudanpi and Xu Changqing.Clinical applications of paeonol are mainly focused on anti-inflammatory effects due to its ability to act as an antioxidant,a regulator of inflammatory enzyme activities,a modulator of inflammatory signaling pathways and a regulator of adhesion molecules to modulate inflammation through molecular mechanisms of action.In addition,paeonol also regulates inflammation by regulating the metabolism of gut microbes.In this review,we searched PubMed,Web of Science,ESI and other websites using“paeonol”“inflammation”“oxidative stress”“signaling pathways”and“gut microbiota”as keywords.We mainly referred to the relevant literature in the last decade and systematically summarized the studies on the anti-inflammatory effects of paeonol to provide a reference for new drug development and clinical application of paeonol.

Apple polyphenol extract alleviates DSS-induced ulcerative colitis and linked behavioral disorders via regulating the gut-brain axis

To explore the effects of apple polyphenol extract(APE)on dextran sulfate sodium(DSS)induced acute ulcer-ative colitis(UC)and linked behavioral disorders,C57BL/6 male mice aged 9-11 weeks were randomly divided into the following groups:(1)Control group(CON),(2)3%DSS group(DSS),(3)3%DSS+APE at 8 a.m.group(DA-ZT0),(4)3%DSS+APE at 8 p.m.group(DA-ZT12).APE was given at a dosage of 500 mg/(kg⋅bw⋅d).APE treatment elevated protein expressions of Occludin,zonula occludins-1(ZO-1)and mucoprotein-2(MUC2),and inhibited inflammatory response by down-regulating the(NOD)-like receptor family and pyrin domain con-taining 3(NLRP3)/apoptosis-associated speck-like protein(ASC)/cysteine aspartate-specific protease-1(caspase-1)signaling pathway.Meanwhile,APE alleviated anxiety and depression-like behavior disorders by upregulating brain-derived neurotrophic factor(BDNF)and postsynaptic-density protein 95(PSD-95)and downregulating allograft inflammatory factor 1(AIF1).Additionally,APE reshaped the structure of the intestinal microbiota,with an increased Firmicutes/Bacterodetes ratio and reduced the relative abundances of Escherichia-Shigella,Bacteroides and Parasutterella.Finally,APE reset DSS-induced circadian rhythm disturbance of clock genes,with significant induction of Cryptochrome2(Cry2),Period2(Per2)and Nuclear receptor subfamily 1 group D member 1(Rev-erbα)in hippocampus and Brain and muscle arnt-like protein 1(Bmal1)and Circadian locomotor output cycles kaput(Clock)in cortex in DA-ZT0 group,but APE treatment at ZT12 induced longer colon length,lower serum IL-βconcentration and proteins expression of NLRP3 and ASC in colon,and better recovery of behavioral disorder.Thus,APE might conserve the potential as a diet-derived nutraceutical for UC treatment.

Effects of foraging site distances on the intestinal bacterial community compositions of the sympatric wintering Hooded Crane(Grus monacha)and Domestic Duck(Anas platyrhynchos domesticus)

Background:The composition of intestinal microflora in animals is affected by cross-species transmission.In a nature reserve,the foraging sites of waterbirds are relatively fixed,but frequently close to residential areas and can also be visited by domestic fowls.It is easy to result in the trans-species-flock dispersal of gut microbes between the wild birds and domestic fowls.The effects of the variable foraging site distances on the gut microbe structures of the waterbirds and the sympatric domestic fowls are currently unclear,and further research is required to evaluate the impacts of geographic location on cross-infection.Methods:Illumina high-throughput sequencing and bioinformatics analysis software were utilized to compare and analyze the composition of gut microbes from the fecal samples of Hooded Cranes(HC;Grus monacha)and two groups of Domestic Ducks(Anas platyrhynchos domesticus)that foraged at 1 km(ducks in near areas,D-N),and 4 km(ducks in far areas,D-F)away from the habitats of the Hooded Cranes at Shengjin Lake,China.Results:The results showed that there were significant differences in the alpha-diversity of the gut bacteria in the HC,D-N,and D-F samples under the interspecific distance factor.The dominant bacterial phyla,Cyanobacteria and Proteobacteria,showed correlations with distance for each host.The D-N group had more diverse intestinal flora than the D-F,as they were physically closer to the HC and had more indirect contact and cross-transmission of their gut microbes.More potentially pathogenic bacterial sequences,and Operational Taxonomic Units(OTUs)were found in the D-N than in HC and D-F.Conclusions:Hooded Cranes and the Domestic Duck populations at variable distances from the cranes showed significant differences in their intestinal bacteria and potentially pathogenic bacteria.The closer the foraging sites were,the easier the intestinal flora spread across species.The results provide a basis for determining the safe distance between wild birds and domestic fowls in a nature reserve.

Gut health:The results of microbial and mucosal immune interactions in pigs

There are a large number of microorganisms in the porcine intestinal tract.These microorganisms and their metabolites contribute to intestinal mucosal immunity,which is of great importance to the health of the host.The host immune system can regulate the distribution and composition of intestinal mi-croorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors,such as mucin,secretory immunoglobulin A(sIgA),regenerating islet-derivedⅢ(RegⅢ)γ,and defensin.Conversely,intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells(Treg)and Th17 cells through their specific components or metabolites.Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function,affecting the health of the body.This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity,discusses the interaction mechanism between the flora and intestinal mucosal immunity,as well as the regulation through fecal microbiota transplantation(FMT),dietary nutritional composition,probiotics and pre-biotics of pig intestinal microecology.Finally,this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.

Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-free Mice

Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms,it may not be possible to replicate human phenotypes in mice through FMT;similarly,treatments that are effective in mouse models may not be effective in humans.In this study,we aimed to identify human gut microbes that undergo significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human–mouse pairs.Strikingly,on average,we found that only 47%of the human gut microbes could be re-established in mice at the species level,among which more than 1/3 underwent significant changes(referred to as“variable taxa”).Most of the human gut microbes that underwent significant changes were consistent across multiple human–mouse pairs and experimental settings.Consequently,about 1/3 of human samples changed their enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed with a controlled diet showed a lower enterotype change rate(23.5%)than those fed with a noncontrolled diet(49.0%),suggesting a possible solution for rescue.Most of the variable taxa have been reported to be implicated in human diseases,with some recognized as the causative species.Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes,provide useful information for researchers using mice in gut microbiota studies,and call for additional validations after FMT.An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.

The role of botanical triterpenoids and steroids in bile acid metabolism,transport,and signaling:Pharmacological and toxicological implications

Bile acids(BAs)are synthesized by the host liver from cholesterol and are delivered to the intestine,where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters.They serve to emulsify dietary lipids and act as signaling molecules,regulating the host’s metabolism and immune homeostasis through specific receptors.Therefore,disruptions in BA metabolism,transport,and signaling are closely associated with cholestasis,metabolic disorders,autoimmune diseases,and others.Botanical triterpenoids and steroids share structural similarities with BAs,and they have been found to modulate BA metabolism,transport,and signaling,potentially exerting pharmacological ortoxicological effects.Here,we have updated the research progress on BA,with a particular emphasis on new-found microbial BAs.Additionally,the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted.Subsequently,the roles of botanical triterpenoids in BA metabolism,transport,and signaling are examined,analyzing their potential pharmacological,toxicological,or drug interaction effects through these mechanisms.Finally,a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

Amino acids in piglet diarrhea:Effects,mechanisms and insights

Piglet diarrhea is among one of the most serious health problems faced by the pig industry,resulting in significant economic losses.Diarrheal disease in piglets has a multifactorial etiology that is affected by physiology,environment,and management strategy.Diarrhea is the most apparent symptom of intestinal dysfunction.As a key class of essential nutrients in the piglet diet,amino acids confer a variety of beneficial effects on piglets in addition to being used as a substrate for protein synthesis,including maintaining appropriate intestinal integrity,permeability and epithelial renewal,and alleviating morphological damage and inflammatory and oxidative stress.Thus,provision of appropriate levels of amino acids could alleviate piglet diarrhea.Most amino acid effects are mediated by metabolites,gut microbes,and related signaling pathways.In this review,we summarize the current understanding of dietary amino acid effects on gut health and diarrhea incidence in piglets,and reveal the mechanisms involved.We also provide ideas for using amino acid blends and emphasize the importance of amino acid balance in the diet to prevent diarrhea in piglets.

A carbon-carbon hydrolase from human gut probiotics Flavonifractor plautii catalyzes phloretin conversion

Although the catabolic pathway of some flavonoids in the human colon has been elucidated,knowledge of related gut microbes and responsible enzymes is still limited.In this study,a phloretin hydrolase gene(phy)from Flavonifractor plautii(F.plautii)was synthesized and heterologously expressed in Escherichia coli BL21(E.coli BL 21).Phloretin hydrolase(PHY)was purified from cell extracts of recombinant E.coli BL21,and PHY's molecular weight was about 32 kDa.The purified PHY effectively cleaved phloretin into 3-(4-hydroxyphenyl)propionic acid(HPPA)and phloroglucinol(PG).PHY's kinetic parameters were determined:Km was 2.8×10−3±0.4 mM and Vmax was 411.2±7.1 U/mg.Besides,PHY's optimal temperature and pH were 50°C and 7.5,respectively,and PHY exhibited 75%activity after 5 h at 50°C.Furthermore,PHY's activity was inhibited in the presence of Ba2+,Cu2+,and Fe2+,while Mg2+slightly elevated PHY's activity.Finally,the catalytic model between phloretin and PHY was built using molecular docking,and PHY's conformational changes were further demonstrated through the multispectral techniques.This study is conducive to understanding phloretin metabolism in the colon and adding a valuable source of PHY for food industry application.

Deterministic processes dominate microbial community assembly in artificially bred Schizothorax wangchiachii juveniles after being released into wild

Fish artificial breeding and release is an important method to restore wild populations of endemic fish species around the world.Schizothorax wangchiachii(SW)is an endemic fish in the upper Yangtze River and is one of the most important species for the artificial breeding and release program implemented in the Yalong River drainage system in China.It is unclear how artificially bred SW adapts to the changeable wild environment post-release,after being in a controlled and very different artificial environment.Thus,the gut samples were collected and analyzed for food composition and microbial 16S rRNA in artificially bred SW juveniles at day 0(before release),5,10,15,20,25,and 30 after release to the lower reaches of the Yalong River.The results indicated that SW began to ingest periphytic algae from the natural habitat before day 5,and this feeding habit is gradually stabilized at day 15.Prior to release,Fusobacteria are the dominant bacteria in the gut microbiota of SW,while Proteobacteria and Cyanobacteria generally are the dominant bacteria after release.The results of microbial assembly mechanisms illustrated that deterministic processes played a more prominent role than stochastic processes in the gut microbial community of artificially bred SW juveniles after releasing into the wild.Overall,the present study integrates the macroscopic and microscopic methods to provide an insight into the food and gut microbial reorganization in the released SW.This study will be an important research direction to explore the ecological adaptability of artificially bred fish after releasing into the wild.

Probiotic Lactobacillus brevis CLB3 prevents azoxymethane/dextran sulfate sodium-induced colon carcinogenesis in mice by reducing amino acid transport and IL-17A levels and repressing the IL-6/AKT/p-STAT3 signaling pathway

Amino acid intake plays a crucial role in the Warburg effect of cancer.Gut microbes can regulate intestinal amino acid metabolism.However,it is still unknown whether probiotic therapy can protect the host from intestinal tumor invasion by reducing amino acid intake.With in vitro methods,three acid-tolerant strains from fermented pickles were screened out.Using azoxymethane/dextran sulfate sodium-induced colon cancer models,we evaluated the therapeutic effects of Lactobacillus brevis CLB3,Lactobacillus plantarum XLP,and Lactobacillus johnsonii CM on model mice.Their functional mechanisms were further explained through anatomy section,quantitative reverse transcription polymerase chain reaction(qRT-PCR),Western blot,and immunohistochemical staining analyses as well as database mining and gut culturomics.The Lactobacillus brevis(L.brevis)CLB3 treatment significantly improved the clinical signs and symptoms of colon cancer,alleviated colon damage,and inhibited colon carcinogenesis in mice.In addition,this treatment significantly increased gut cultivable Lactobacillus abundance,inhibited the expression and translation levels of the tumor metabolism-related solute carrier(SLC)amino acid transporter including SLC7A5 and SLC7A11,lowered circulating interleukin-6(IL-6)and interleukin-17A(IL-17A)levels,and improved the accumulation of tumor-infiltrating lymphocytes and cancer proliferation factors.These findings suggest that L.brevis CLB3 can reduce amino acid transport,inhibit mammalian target of rapamycin(mTOR)signaling and enhance intestinal anti-tumor immune responses,which provides a potential targeting amino acid transporter strategy for preventing colorectal cancer.

Dietary fiber and microbiota interaction regulates sow metabolism and reproductive performance

Dietary fiber is a critical nutrient in sow diet and has attracted interest of animal nutritionists for many years.In addition to increase sows’satiety,dietary fiber has been found to involve in the regulation of multiple biological functions in the sow production.The interaction of dietary fiber and gut microbes can produce bioactive metabolites,which are of great significance to sows’metabolism and reproductive performance.This article reviewed the interaction between dietary fiber and gut microbes in regulating sows’gut microbial diversity,intestinal immune system,lactation,and production performance,with the aim to provide a new strategy for the use of dietary fiber in sow diets.