Traditional Chinese Medicine in Treatment of Constipation Based on 5-HT Signaling Pathway： A Review / 中国实验方剂学杂志

Chronic constipation （CC） is one of the most common functional gastrointestinal diseases. At present， the overall therapeutic effect of CC is still not satisfactory worldwide， which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity， social psychology， diet， intestinal flora imbalance， intestinal motility disorder， visceral sensitivity change， pelvic floor muscle group dysfunction and enteric nervous system （ENS） disorder. Among them， the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain， integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it， and can communicate with the intestinal tract and the central nervous system through nerve， endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis， 5-hydroxytryptamine （5-HT） is involved in the regulation of gastrointestinal motility， sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine（TCM） is a unique precious resource in China， which has good curative effects and safety. In recent years， it has received extensive attention in the treatment of constipation. TCM and active ingredients， acupuncture and massage specifically regulate 5-HT signal transmission， so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms， with unique advantages. Therefore， this study used ''constipation''， ''intestinal flora''， ''5-HT''， and ''traditional Chinese medicine'' as the keywords to search PubMed， China National Knowledge Infrastructure （CNKI） and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data / 中南大学学报(医学版)

OBJECTIVES@#Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms.@*METHODS@#Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants.@*RESULTS@#MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH.@*CONCLUSIONS@#There is a causal association and pleiotropic variants between GM and ICH.

Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method / 中华老年医学杂志

Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.

Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism / 中国天然药物

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.

The microbiota-gut-brain axis and neurodevelopmental disorders

The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.

Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Cambios en la microbiota durante el embarazo: revisión narrativa / Changes in the microbiota during pregnancy: a narrative review

OBJETIVO: Evaluar la evidencia científica de los cambios en la microbiota durante el embarazo. METODOLOGÍA: Revisión de la bibliografía publicada entre el 2013 y el 2022 efectuada mediante la búsqueda de artículos científicos escritos en español e inglés resguardados en las bases de datos bibliográficas NICE, CENETEC-SALUD, BIREME y Portal OMS, OPS, Portal de Evidencias de la Biblioteca Virtual de Salud - BVS, LILACS, BIREME, EVIPNET, PubMed y Cochrane. La selección de artículos se basó en los descriptores: microbiota; embarazo-pregnancy; microbiota, gut microbiome, fetus-feto; microbiota, placenta; microbiota, combinadas entre sí con el operador boleano "and". RESULTADOS: Se identificaron 3038 posibles artículos y 137 se encontraron adecuados para el objetivo de la revisión en virtud de estar relacionados directamente con el embarazo y la microbiota. Se revisaron estudios transversales, ensayos, revisiones, cohortes, casos y controles, revisiones sistemáticas o matanálisis. CONCLUSIONES: La microbiota se encuentra en diversos tejidos u órganos que anteriormente se creían estériles durante el embarazo. Se sugiere que todos los cambios que implica esta etapa pueden influir en la microbiota de la madre y el feto. A pesar de las crecientes investigaciones en el área aún quedan preguntas por contestar para ayudar a solucionar el enigma de los cambios en la diversidad en las diferentes complicaciones del embarazo y saber si los probióticos tendrían efecto o no en la disminución del riesgo a padecerlas.

Abstract OBJECTIVE: to evaluate the scientific evidence on changes in the microbiota during pregnancy. METHODOLOGY: A review of the literature published between 2013 and 2022 was carried out through the search of scientific articles in Spanish and English in the bibliographic databases NICE, CENETEC-SALUD, BIREME AND PORTAL WHO, PAHO, Portal of Evidence of the Virtual Health Library - BVS, LILACS, BIREME, EVIPNET, PUBMED and COCHRANE. The selection of articles was based on the descriptors: Microbiota, pregnancy, Gut microbiome, Fetus-Microbiota, Placenta - Microbiota, combined with each other with the Boolean "and". RESULTS: A total of 3,038 possible articles were identified and 137 were found suitable for the objective of the review because they were directly related to pregnancy and microbiota. Cross-sectional studies, trials, reviews, cohorts, case-controls, systematic review, or meta-analysis were reviewed. CONCLUSIONS: Microbiota has been found in various tissues or organs that were previously believed to be sterile during pregnancy, and with this, it is suggested that all the changes that this stage entails can influence the maternal and fetal microbiota. However, despite the growing research in the area, there are still questions to be resolved to help solve the enigma of the changes in diversity in the different complications of pregnancy and whether the use of probiotics would influence reducing the risk to present them.

Heavy metal resistance in the Yanomami and Tunapuco microbiome

BACKGROUND The Amazon Region hosts invaluable and unique biodiversity as well as mineral resources. Consequently, large illegal and artisanal gold mining areas exist in indigenous territories. Mercury has been used in gold mining, and some has been released into the environment and atmosphere, primarily affecting indigenous people such as the Yanomami. In addition, other heavy metals have been associated with gold mining and other metal-dispersing activities in the region. OBJECTIVE Investigate the gut microbiome of two semi-isolated groups from the Amazon, focusing on metal resistance. METHODS Metagenomic data from the Yanomami and Tunapuco gut microbiome were assembled into contigs, and their putative proteins were searched against a database of metal resistance proteins. FINDINGS Proteins associated with mercury resistance were exclusive in the Yanomami, while proteins associated with silver resistance were exclusive in the Tunapuco. Both groups share 77 non-redundant metal resistance (MR) proteins, mostly associated with multi-MR and operons with potential resistance to arsenic, nickel, zinc, copper, copper/silver, and cobalt/nickel. Although both groups harbour operons related to copper resistance, only the Tunapuco group had the pco operon. CONCLUSION The Yanomami and Tunapuco gut microbiome shows that these people have been exposed directly or indirectly to distinct scenarios concerning heavy metals.

Effects of gut microbiome imbalance on impaired cognitive function in patients with schizophrenia / 四川精神卫生

The objective of this study is to elucidate the effects of gut microbiome imbalance on impaired cognitive function in schizophrenia patients， and to propose a new approach to improve cognitive impairment in schizophrenia patients. The cognitive impairment of schizophrenic patients is one of the major barriers that hinder patient social reintegration. With the emergence of microbiome-gut-brain axis， many researchers have found that there is a certain relationship between gut microbiome imbalance and impaired cognitive function in schizophrenia patients， so this paper reviews and summarizes such relationship found in previous studies， with a view to informing the exploration of new ways to improve cognitive impairment in schizophrenia patients.

Research progress about the effect of gut microbiome on the formation process of calcium oxalate stone through gut-kidney axis / 中华泌尿外科杂志

Calcium oxalate (CaOx) stone is the main type, and its formation is closely related to the metabolism of oxalic acid and calcium. Gut Microbiome is normal microflora which settled in the human intestinal tract and plays an important role in regulating a variety of metabolism in the body. In the past, Oxalobacter formigenes in gut was a protective factor for the formation of CaOx stones. Recently, it has been found that the bacteria regulating oxalate metabolism were not limited to Oxalobacter formigenes. Gut Microbiome of CaOx stones formers is different from healthy people. It regulates the metabolism of oxalic acid in the body through the gut-kidney axis and affect the formation of CaOx stone. The purpose of this study is to describe the characteristics of intestinal flora in patients with CaOx stones, and to summarize its potential function in the formation of CaOx stones and its possible clinical application in the future.

Integrated analysis of gut microbiome and host immune responses in COVID-19 / 医学前沿

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

Biomarkers of gastrointestinal dysfunction in children / 中国小儿急救医学

Due to incomplete function of gastrointestinal barrier, children are more likely to develop gastrointestinal dysfunction.The clinical application of related biomarkers helps early diagnosis and treatment of gastrointestinal dysfunction in children.By sorting out the studies in recent years, we explored the relationship between inflammatory indicators, intestinal epithelial barrier damage biomarkers, immunological biomarkers, gut microbiome and gastrointestinal dysfunction, and summarized the main problems and solutions faced in the research, which may help the screening, identification and clinical application of relevant biomarkers in subsequent research.

Progress of Research on Gut Mycobiome and Chronic Liver Diseases / 胃肠病学

Gut mycobiome plays an important role in host’s health, and many chronic liver diseases are accompanied by gut fungi disorder. Gut mycobiome is involved in the development of liver diseases through direct colonization or indirectly through its metabolites and various regulatory factors. Regulation of intestinal fungi may provide a new strategy for the treatment of chronic liver disease. This article reviewed research methods for gut fungi and compositional changes in fungi associated with chronic liver diseases, explored the impact of gut mycobiome on liver disease pathogenesis, assessed its potential utility as therapeutic target,and objected to provide a reference for further research on liver diseases and gut mycobiome. Future researches should further explore the characteristics of intestinal fungi and their metabolites in various liver diseases so as to provide new methods for the prevention, diagnosis, and treatment of liver diseases.

Fish Oil Improves Dysbiosis of Host-microbial Interaction and Maintains Remission in Colitis Mice / 中国生物化学与分子生物学报

n-3 polyunsaturated fatty acids (PUFAs) play an active role in controlling the progression of ulcerative colitis (UC), but its mechanism is not very clear. In this study, we compared the effects of fish oil (the main component is n-3 PUFAs) in the mouse model with acute and chronic colitis induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were randomly divided into six groups, and each group had ten mice. The alleviating effect of fish oil on chronic colitis was significantly better than acute colitis as indicated by the following analysis: the weight loss of mice (P < 0. 05), decreased disease activity index (DAI) score (P<0. 05), colonic edema, colon length index and histopathological score (P < 0. 05), and serum pro-inflammatory factor levels like IL-1β, TNF-α, and IL-6 (P < 0. 01). Moreover, fish oil promoted the level of serum anti-inflammatory factor IL-10 (P<0. 05). The treatment of fish oil increased the n-3 PUFA concentration in the intestinal epithelium of mice (P < 0. 01), especially EPA (P<0. 05). 16S rRNA sequencing of feces revealed that fish oil significantly increased the relative abundance of butyrate-producing flora (Clostridiales) and probiotics (Bifidobacteriales) in the feces of the maintained remission model group, reduce the proportion of aerobic, parthenogenic anaerobic and pathogenic, and improved the disorder of glycan biosynthesis and metabolism and oxidative phosphorylation (P<0. 05). Compared with the induced remission fish oil group, fish oil treatment led to an elevated expression of mechanical barrier and energy metabolism pathway proteins in the maintained remission fish oil group. Our results showed that fish oil exerted a more potent inhibitory effect in the remission mice model, which may be related to effectively strengthening the mechanical barrier, improving the composition and function of intestinal microbiota and concentration of butyric acids and improving dysbiosis of host-microbial interaction.

Comprehensive Evaluation and Application of Experimental Sources of Variation in Gut Microbiome Sequencing Studies / 中国生物化学与分子生物学报

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

Research Progress on Effects of Gut Microbiome on Efficacy of Immune Checkpoint Inhibitors in Colorectal Cancer / 肿瘤防治研究

With the rapid development of immunotherapy, an increasing number of immune checkpoint inhibitors have been used in clinical settings. Immunotherapy provides a new treatment option for patients with advanced colorectal cancer metastasis. Studies have confirmed that patients with metastatic colorectal cancer with dMMR/MSI-H status are more sensitive to immunotherapy and have a more objective and sustained clinical response than their counterparts. Gut microbiome has been proved to play a certain regulatory role in tumor immunotherapy response, and some bacteria can affect the efficacy of immune checkpoint inhibitors through the immune system or metabolic function of the body. With the progress of the study, the gut microbiome is expected to become not only the predictive biomarkers of curative effect of colorectal cancer immunotherapy, but it can also be a key regulatory factor influencing the results of colorectal cancer immunotherapy. For future clinical treatment, the use of immune checkpoint inhibitors may benefit patients with advanced colorectal cancer.

Progress on Correlation Between Type 2 Diabetes Mellitus and Malignant Tumors / 肿瘤防治研究

Type 2 diabetes mellitus and malignant tumors are two kinds of chronic diseases with tremendous impact on human health. Numerous epidemiological and clinical studies have shown that type 2 diabetes mellitus increases the risk of liver, pancreatic, endometrial, gallbladder, colorectal and breast cancers. Hyperglycemia can promote cancer cell proliferation, migration, invasion and immune escape through a variety of direct and indirect mechanisms. Insulin resistance and hyperinsulinemia can activate multiple signal transduction pathways through insulin/IGF-I signaling axis and promote tumorigenesis. Sustained chronic inflammatory responses can promote the development of cancer through DNA damage and pro-inflammatory factors. Gut microbiome dysbiosis is closely related to the occurrence of several gastrointestinal tumors. This paper reviews the progress on the correlation between type 2 diabetes mellitus and the progression of malignant tumors and the possible mechanisms.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.