Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Mechanism of Bushen Yijing Method in Treatment of Oligoasthenozoospermia Based on Intestinal Microbiota / 中国实验方剂学杂志

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

Research progress on the regulation of intestinal flora and effect on intestinal absorption and transport by TCM components / 药学实践杂志

The domestic and international research progress on the regulation of gut microbiota by Traditional Chinese Medicine (TCM) ingredients and their impact on intestinal absorption and transportation were summarized, which provided assistance for subsequent clinical rational drug use targeting gut microbiota. Literature on the relationship between gut microbiota and intestinal absorption and transportation in recent years were reviewed and analyzed, and the mechanism of TCM ingredients regulating gut microbiota on drug absorption and transportation was elucidated. Research has found that TCM ingredients alter gut microbiota, thereby affecting intestinal barrier function and absorption of transport proteins, which is of great significance for rational clinical medication.

Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5 / 环境与职业医学

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Fatores dietéticos e microbianos que interferem no tratamento da osteoartrite / Dietary and microbial factors that interfere in the treatment of osteoarthritis / Factoresdietéticos y microbianos que interfieren en el tratamento de la artroses

Introdução:A osteoartrite é uma doença degenerativa caracterizada pela deterioração progressiva da cartilagem articular, resultando em dor e incapacidade articular total em estágios avançados.Éconsiderada um dos distúrbios articulares mais comuns em todo o mundo e sua prevalência está aumentando constantemente devido ao envelhecimento, dietas inflamatórias e inatividade física. Objetivo:Investigar a contribuição da microbiota intestinal e dos componentes dietéticos, naperspectiva dediminuir as patologias associadas à osteoartrite. Metodologia:Trata-se de uma revisão integrativa desenvolvida a partir da seleção de artigos disponíveis escritos nalíngua inglesa, publicados nas bases de dados Pubmed e Science Direct. Resultados:No total, 25.583 artigos foram encontrados na busca, após os critérios de exclusão, 19 artigos compuseram o corpo de análise da revisão. Pesquisas em animais mostram que os efeitos induzidos por dieta rica em gordura foram evidentes e indicaram uma inflamação sistêmica de baixo grau resultando no agravamento da oesteoartritepor meio do aumento da degeneração da cartilagem. Dado ao impacto potencial da dieta na oesteoartrite, foram realizados estudos para avaliar a dieta mediterrânea, os níveis de ômega 3 e 6, vitamina C e E, com destaque para a oligofrutose, uma abordagem nova para tratar a oesteoartriteda obesidade. Conclusões:Conclui-se que apesar de já existir alguma evidência da utilidade da nutrição por meioda dieta alimentar como complemento da terapêutica na osteoartrite são necessários mais estudos que comprovem as intervenções na redução máxima dos marcadores inflamatórios ocasionando o alíviodos sintomas em pacientes com oesteoartrite (AU).

Introduction:Osteoarthritis is a degenerative disease characterized by progressive deterioration of the articular cartilage, resulting in pain and total joint disability in advanced stages. It is considered one of the most common joint disorders worldwide and its prevalence is steadily increasing due to aging, inflammatory diets and physical inactivity. Objective:The aim of this literature review was to investigate the contribution of intestinal microbiota and dietary components to try to reduce the pathologies associated with osteoarthritis.Methodology:This is an integrative review, developed from the selectionof available articles written in English, published in the Pubmed and Science Direct databases. Results:Intotal, 25.583articleswerefoundinthesearch,aftertheexclusioncriteria,19 articles madeupthebodyofanalysisofthereview.Animal research shows that the effects induced by a high-fat diet were evident and indicated low-grade systemic inflammation resulting in worsening osteoarthritis by increasing cartilage degeneration. Given the potential impact of diet on osteoarthritis, studies have been conducted to evaluate the Mediterranean diet, omega 3 and 6 levels, vitamin C and E, especially oligofructose, a new approach to treat obesity osteoarthritis.Conclusions:It is concluded that although there is already some evidence of the usefulness of nutrition through the diet as a complement to therapy in osteoarthritis, further studiesare needed to prove the interventions in the maximum reduction of inflammatory markers will cause the relief of symptoms in patients with osteoarthritis (AU).

Introducción: La artrosis es una enfermedad degenerativa caracterizada por el deterioro progresivo del cartílago articular, que se traduce en dolor e incapacidad articular total en estadios avanzados. Se considera uno de los trastornos articulares más comunes en todo el mundo y su prevalencia aumenta constantemente debido al envejecimiento, las dietas inflamatorias y la inactividad física. Objetivo: El objetivo de esta revisión fue investigar la contribución de la microbiota intestinal y los componentes de la dieta, en un intento por reducirlas patologías asociadas a la artrosis. Metodología: Se trata de una revisión integradora, desarrollada a partir de la selección de artículos disponibles escritos en inglés, publicados en las bases de datos Pubmed y Science Direct. Resultados: En total, se encontraron 25.583 artículos en la búsqueda, después de los criterios de exclusión, 19 artículos conformaron el cuerpo de análisis de la revisión.La investigación en animales muestra que los efectos inducidos por una dieta alta en grasas fueron evidentes e indicaron una inflamación sistémica de bajo grado que resultó en un empeoramiento de la osteoartritis a través de una mayor degeneración del cartílago. Dado el impacto potencial de la dieta en la osteoartritis, se han realizado estudios para evaluar ladieta mediterránea, los niveles de omega 3 y 6, vitamina C y E, con énfasis en la oligofructosa, un nuevo enfoque para tratar la osteoartritis por obesidade.Conclusiones: Se concluye que aunque ya existe alguna evidencia de la utilidad de la nutrición a través de la dieta como complemento al tratamiento de la artrosis, son necesarios más estudios que prueben intervenciones en la reducción máxima de los marcadores inflamatorios, provocando el alivio de los síntomas en pacientes con osteoartritis (AU).

Microbiota intestinal y cólicos infantiles: ¿hay lugar para los prebióticos, probióticos y posbióticos? / Gut Microbiota and Infant Colic: is there a Place for Prebiotics, Probiotics, and Postbiotics?

El consumo de probióticos, prebióticos y posbióticos, o su combinación, puede contribuir a mantener una microbiota intestinal saludable ya que permite la regulación de su disbiosis en el caso de algunas enfermedades o trastornos, principalmente en los trastornos gastrointestinales funcionales (TGIF). El microbioma intestinal es protagonista esencial en la fisiopatología de los TGIF a través de sus funciones metabólicas y nutricionales, el mantenimiento de la integridad de la mucosa intestinal y la regulación de la respuesta inmunitaria. Las investigaciones realizadas hasta la fecha indican que los probióticos, prebióticos y posbióticos pueden tener efectos inmunomoduladores directos y clínicamente relevantes. Existen pruebas del uso de esta familia de bióticos en individuos sanos para mejorar la salud general y aliviar los síntomas en una serie de enfermedades como los cólicos infantiles. La colonización y establecimiento de la microbiota comienza en el momento del nacimiento; los primeros 2-3 años de vida son fundamentales para el desarrollo de una comunidad microbiana abundante y diversa. Diversos estudios científicos realizados mediante técnicas tradicionales dependientes de cultivo y más recientemente por técnicas moleculares han observado diferencias en las poblaciones bacterianas de bebés sanos y aquellos que sufren TGIF, estos últimos caracterizados por un aumento de especies patógenas y una menor población de bifidobacterias y lactobacilos, en comparación con los primeros. En tal contexto, se considera que la microbiota intestinal como protagonista en el desarrollo de esos trastornos, entre ellos los cólicos infantiles, a través de sus funciones metabólicas, nutricionales, de mantenimiento de la integridad de la mucosa intestinal y regulación de la respuesta inmunitaria. Esto ha abierto la puerta al estudio de la utilización de prebióticos, probióticos y posbióticos en el tratamiento y/o prevención de los TGIF infantiles. El parto vaginal y de término así como la lactancia son fundamentales en la constitución de una microbiota saludable. Como herramientas de apoyo, existen estudios de eficacia que sustentan la administración de esta familia de bióticos, principalmente en los casos en que la lactancia no sea posible o esté limitada. (AU)

The consumption of probiotics, prebiotics, and postbiotics, or a combination of them, can contribute to maintaining a healthy intestinal microbiota as it allows the regulation of its dysbiosis in the case of some diseases or disorders, mainly in functional gastrointestinal disorders (FGIDs). The gut microbiome is an essential player in the pathophysiology of FGIDs through its metabolic and nutritional functions, the maintenance of intestinal mucosal integrity, and the regulation of the immune response. Research results thus far indicate that probiotics, prebiotics, and postbiotics may have direct and clinically relevant immunomodulatory effects. There is evidence regarding the prescription of this family of biotics in healthy individuals to improve overall health and alleviate symptoms in many conditions like infantile colic. The colonization and microbiota establishment begins at birth; the first 2-3 years of life are critical for developing an abundant and diverse microbial community. Several scientific studies performed by traditional culture-dependent techniques and more recently by molecular techniques have observed differences in the bacterial populations of healthy infants and those suffering from FGIDs, the latter characterized by an increase in pathogenic species and a lower population of bifidobacteria and lactobacilli, compared to the former. In this context, the intestinal microbiota plays a leading role in the onset of these disorders, including infantile colic, through its metabolic and nutritional functions, maintenance of the integrity of the intestinal mucosa, and regulation of the immune response. That has opened the door to the study of prebiotics, probiotics, and postbiotics usage in the treatment and or prevention of infantile FGIDs. Vaginal and term delivery and breastfeeding are fundamental in the constitution of a healthy microbiota. As supportive tools, there are efficacy studies that support the administration of this family of biotics, mainly in cases where lactation is not possible or is limited.

Efficacy of Bacillus clausii in Pediatric Functional Constipation: A Pilot of a Randomized, Double-Blind, Placebo-Controlled Trial

Purpose: To evaluate the efficacy of Bacillus clausii in the treatment of pediatric constipation. Methods: A randomized, double-blind, placebo-controlled trial was conducted from January, 2021 to January, 2022 in children aged 1-5 years diagnosed with functional constipation according to Rome IV criteria. They were assigned to receive either B. clausii or placebo, once daily for four weeks. The primary out-come was treatment success (defined as ?3 spontaneous stools per week and stool consistency grade ?3 on Bristol stool chart). The secondary outcome was a comparison of stool frequency, consistency (defined by Bristol stool grade), and constipationrelated symptoms. Results: This trial enrolled 38 children (B. clausii, n=20 and placebo, n=18). At 4 weeks, no significant difference was noted in the treatment success between B. clausii and placebo groups [45% vs 56%; P=0.52). On within-group analyses, the mean (SD) of Bristol stool grade increased in both the B. clausii [1.7 (0.5) to 2.8 (1.2); P=0.003] and placebo [1.8 (0.5) to 2.8 (1.2); P=0.01] groups. Significant increases in the treatment success rate (22% to 56%, P=0.01) and mean stool frequency per week [3 (0.9) to 4.2 (1.7), P=0.01] were pronounced only in the placebo group. The frequency of painful defecation and large fecal mass were also significantly decreased in both the groups. No serious adverse events were observed. Conclusion: A 4-week course of B. clausii as the sole treatment was not more effective than a placebo for the management of functional constipation in children aged 1-5 years.

Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine” / 中山大学学报(医学科学版)

ObjectiveTo investigate whether the whole intestinal microbiota transplantation in Alzheimer's disease （AD） model mice has more significant effects on ileum intestinal microenvironment in normal mice under the guidance of the theory of traditional Chinese medicine that "interior-exterior relationship exists between the heart and small intestine". MethodsThe whole intestinal microbiota of fourteen 6-month-old specific pathogen free male APP/PS1 double-transgenic AD model mice was transplanted into the gut of six normal C57BL/6J mice of the same age and background treated with mixed antibiotics for 14 days. Then， after 14 days of normal rearing， the mice were sacrificed. Next， the pathological changes in the ileum and colon were observed， and the composition and diversity of the ileal and colonic microbiota was analyzed by sequencing. ResultsAfter the whole intestinal microbiota of AD mice was transplanted into normal mice， pathological analysis showed that only the ileum tissue had mucosal damage and crypt gland epithelial cell degeneration， necrosis， and shedding. Moreover， the microbiota analysis found that only the number of genera （P<0.01）， Chao1 index （P<0.01） and Simpson index of ileal microbiota in normal mice decreased （P<0.01）， and the composition of intestinal microbiota was quite similar to that of AD model mice. ConclusionUnder the effect of whole gut microbiota transplantation in AD mice， the diversity and composition of ileal microbiota change more than that of colonic microbiota in normal mice， and at the same time， it results in pathological damage to the ileal mucosa， indicating that the ileal microenvironment may be more closely related to the occurrence and development of AD， which is highly consistent with the traditional Chinese medicine theory of "interior-exterior relationship between heart and small intestine".

Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI.@*METHODS@#In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups.@*RESULTS@#Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05).@*CONCLUSIONS@#There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Intestinal and pharyngeal microbiota in early neonates: an analysis based on high-throughput sequencing / 中国当代儿科杂志

OBJECTIVES@#To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates.@*METHODS@#Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared.@*RESULTS@#The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05).@*CONCLUSIONS@#The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.

Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Comparison of bacterial and human drug metabolizing enzymes in database and prospect of influence of intestinal bacteria on drug metabolism / 中国药科大学学报

@#This study focused on various databases and literatures related to drug metabolism, collated and analyzed the information related to bacterial and human drug metabolic enzymes, and compared the similarities and differences between the information included in the database of bacterial and human drug metabolic enzymes. Results found more bacterial drug metabolic enzymes than human drug metabolic enzymes (9 703 vs 964), but much less than the total number of bacterial enzymes in BRENDA database (9 703 vs 20 835 235), indicating that the influence of bacteria on drug metabolism could have been greatly underestimated, and that further systematic research is needed.We summarized the progress and shortcomings of the current research on the influence of intestinal flora on drug metabolism, and proposed a research idea, that is, to predict through artificial intelligence whether intestinal bacterial proteins have the ability to metabolize drugs, to verify their biological functions by in vitro/in vivo experiments and gene editing, and to establish a database of drug metabolic enzymes from intestinal bacteria with complete annotation functions, in an attempt to provide a solid theoretical basis for further exploration of the effects of intestinal flora on drug metabolism.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.@*METHODS@#This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.@*RESULTS@#Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.@*CONCLUSION@#BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation / 中华血液学杂志

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Effect of intestinal Metrnl gene knockout on intestinal microbiota and ulcerative colitis / 药学实践杂志

Objective To investigate the effect of intestinal Metrnl on dextran sodium sulfate (DSS)-induced ulcerative colitis mouse model and the regulation mechanism of intestinal microbiota. Methods Different concentrations of DSS (3% DSS and 1% DSS) were used to induce ulcerative colitis on C57 mice to determine the experimental conditions. Intestinal epithelial Metrnl specific knockout mice (Metrnl(-/-)) and its control mice (Metrnl(+/+)) were administrated with 3% DSS for 5 d. Then the survival time, body weight, DAI (disease activity index), colon length and pathological changes in colon tissues were observed. 16S ribosomal RNA gene sequencing was used to detect the composition of intestinal microbiota. Results Compared with 1% DSS, 3% DSS could significantly aggravate ulcerative colitis on C57 mice, such as lower survival rate (P<0.05), more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). After administrated to 3% DSS for 5 d, comparing with Metrnl(+/+) mice, Metrnl(-/-) mice showed more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). The 16S ribosomal RNA results showed that the diversity of intestinal microbiota in Metrnl(-/-) mice significantly decreased. Furthermore, Bacteroidetes and Proteobacteria significantly decreased, while Firmicutes increased. Conclusion Metrnl could protect the DSS-induced ulcerative colitis mouse through regulating intestinal microbiota.

Effects of Tongfengning（痛风宁） on Intestinal Flora and Intestinal Uric Acid Metabolism in Model Mice of Hyperuri⁃cemia of Spleen Deficiency with Exuberance of Dampness Syndrome / 中医杂志

ObjectiveTo explore the possible mechanisms of Tongfengning （痛风宁， TFN） in treating hyperuricemia （HUA） of spleen deficiency with exuberance of dampness syndrome. MethodsTen of 60 mice were randomly selected， and were fed with regular diet as the control group， while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness. After the successful modeling， in order to better observe the effects of TFN on the intestinal microbiota of the model mice， a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice. Fifty sucessfully modeled mice were randomly divided into model group， TFN group， allopurinol group， probiotics group， and an allopurinol + probiotics group， 10 in each group. The TFN group was administered TFN liquid at a dosage of 19.11 g/（kg·d） by gavage. The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/（kg·d） by gavage. The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/（kg·d） and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The control group and model group were administered normal saline at a dosage of 19.11 ml/（kg·d） by gavage. The interventions were continued for 21 days. In order to maintain a stable high blood uric acid state， all groups but the control group continued modeling while receiving drug intervention. The changes in spleen deficiency syndrome scores， blood uric acid levels， microbial community structure， acetic acid and butyric acid content in intestinal lavage fluid， adenosine deaminase （ADA） and xanthine oxidase （XOD） content in small intestine tissue， as well as ATP-binding cassette transporter G2 （ABCG2）， glucose transporter 9 （GLUT9） protein and mRNA expression in the small intestine tissue were compared among the groups of mice. ResultsCompared with the control group， the model group showed increased spleen deficiency syndrome scores， blood uric acid levels， relative abundance of phylum Firmicutes， Firmicutes/Bacteroidetes ratio， abundance of Bacteroides genus， Klebsiella genus， and Enterococcus genus， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， as well as GLUT9 protein and mRNA expression （P<0.05）. The number of operational taxonomic units （OTUs） of intestinal microbiota， relative abundance of Bacteroidetes phylum， abundance of Lactobacillus genus and uncultured Bacteroides genus， butyric acid content in intestinal lavage fluid， and ABCG2 protein and mRNA expression in small intestine tissue were significantly decreased （P＜0.05）. Compared with the model group， in the group treated with TFN， probiotics， and allopurinol + probiotics， the spleen deficiency syndrome score， blood uric acid level， relative abundance of Firmicutes， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， GLUT9 protein and mRNA expression significantly decreased. The number of gut microbiota OTUs， relative abundance of proteobacteria， butyric acid content in intestinal lavage fluid， ABCG2 protein and mRNA expression in small intestine tissue significantly increased （P＜0.05）. In the probiotics group， the ratio of Firmicutes to Bacteroidetes decreased. In the TFN group， the abundance of Lactobacillus and uncultured Bacteroidetes significantly increased， while the abundance of Parabacteroides， Klebsiella， and Enterococcus significantly decreased （P＜0.05）. Compared with the TFN group， allopurinol group and the probiotics group showed elevated blood uric acid levels， abundance of Bacteroidetes， ADA and XOD levels in intestinal tissue， and GLUT9 mRNA expression. The relative abundance of Firmicutes， abundance of lactobacilli， and ABCG2 mRNA expression significantly decreased. The probiotics group showed elevated GLUT9 protein expression in intestinal tissue. The probiotics group and the allopurinol plus probiotics group showed significantly higher scores for spleen deficiency syndrome in mice， and lower levels of butyric acid in mouse intestinal lavage fluid. The allopurinol group showed decreased numbers of OTUs in mouse intestinal flora， decreased abundance of proteobacteria， and butyric acid levels in intestinal lavage fluid. The allopurinol group also showed decreased ABCG2 protein expression in intestinal tissue， increased acetic acid levels in intestinal lavage fluid， increased abundance of Klebsiella， and significantly elevated GLUT9 protein expression （P＜0.05）. ConclusionsThe treatment of HUA with TFN may be associated with the regulation of intestinal probiotics （such as lactobacilli） and pathogenic bacteria （such as Klebsiella）， as well as the production of bacterial metabolites such as acetic acid and butyric acid. It may also involve reducing the expression of ADA and XOD in the intestines， decreasing intestinal uric acid production， upregulating the expression of intestinal epithelial urate transporter ABCG2， downregulating GLUT9 expression， and promoting intestinal uric acid excretion. These factors are related to the syndrome of spleen deficiency with exuberance of dampness.

Research progresses on the role of short-chain fatty acids in the pathogenesis of Parkinson′s disease / 中华神经科杂志

In recent years, a number of studies have found that the dysregulation of intestinal microbes and their metabolites plays an important role in the occurrence and development of Parkinson′s disease (PD), and is closely related to the severity of PD clinical symptoms. Short-chain fatty acids are the main metabolites of intestinal microorganisms and may be involved in the pathogenesis of PD by regulating the inflammatory response, neuronal autophagy and apoptosis and the integrity of the blood-brain barrier and intestinal barrier. In this paper, the research progresses on the role of short-chain fatty acids in the pathogenesis of PD are reviewed, in order to provide new ideas for the treatment of PD.

Intestinal microbiota and pediatric inflammatory bowel disease / 中国小儿急救医学

Inflammatory bowel disease is a chronic recurrent inflammatory disease of the intestine of unknown origin.It is currently thought to be mediated by a combination of susceptibility genes, intestinal microecology and immune involvement, with all three interacting and influencing each other.This leads to a disruption of the intestinal microenvironment, which affects the host′s immune tolerance, and ultimately induces intestinal inflammation.In this review, we summarized the mechanisms of intestinal microbiota in children with inflammatory bowel disease and discussed new ideas of microecological agents for individualized treatment of children with inflammatory bowel disease.

S1P/S1P Receptor Pathway: A New Target for Treatment of Inflammatory Bowel Disease / 胃肠病学

The development of targeted oral drugs that can stably treat inflammatory bowel disease (IBD) is still a clinical problem to be solved. In recent years, studies have confirmed that sphingosine⁃1⁃phosphate (S1P)/S1P receptor pathway can regulate lymphocyte homing and immune regulation, inhibit intestinal inflammation, protect intestinal endothelial barrier, and affect intestinal microbial metabolism, which may play a key role in the treatment of IBD. This article reviewed the effect of S1P/S1P receptor pathway on IBD and its potential mechanism.