Gastrointestinal microbiome and cholelithiasis:Current status and perspectives

Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.

Immuno-oncology-microbiome axis of gastrointestinal malignancy

Research on the relationship between the microbiome and cancer has been controversial for centuries.Recent works have discovered that the intratumor microbiome is an important component of the tumor microenvironment(TME).Intratumor bacteria,the most studied intratumor microbiome,are mainly localized in tumor cells and immune cells.As the largest bacterial reservoir in human body,the gut microbiome may be one of the sources of the intratumor microbiome in gastrointestinal malignancies.An increasing number of studies have shown that the gut and intratumor microbiome play an important role in regulating the immune tone of tumors.Moreover,it has been recently proposed that the gut and intratumor microbiome can influence tumor progression by modulating host metabolism and the immune and immune tone of the TME,which is defined as the immuno-oncology-microbiome(IOM)axis.The proposal of the IOM axis provides a new target for the tumor microbiome and tumor immunity.This review aims to reveal the mechanism and progress of the gut and intratumor microbiome in gastrointestinal malignancies such as esophageal cancer,gastric cancer,liver cancer,colorectal cancer and pancreatic cancer by exploring the IOM axis.Providing new insights into the research related to gastrointestinal malignancies.

Role of calcium and other trace elements in the gastrointestinal physiology

Calcium is an essential ion in both marine and terrestrial organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the regulation of neuronal function. The Ca^2＋ balance is maintained by three organ systems, including the gastrointestinal tract, bone and kidney. Since first being cloned in 1993 the Ca^2＋-sensing receptor has been expressed along the entire gastrointestinal tract, until now the exact function is only partly elucidated. As of this date it still remains to be determined if the Ca^2＋-sensing receptor is involved in calcium handling by the gastrointestinal tract. However, there are few studies showing physiological effects of the Ca^2＋-sensing receptor on gastric acid secretion and fluid transport in the colon. In addition, polyamines and amino acids have been shown to activate the Ca^2＋-sensing receptor and also act as allosteric modifiers to signal nutrient availability to intestinal epithelial cells. Activation of the colonic Ca^2＋-sensing receptor can abrogate cyclic nucleotide-mediated fluid secretion suggesting a role of the receptor in modifying secretory diarrheas like cholera. For many cell types changes in extracellular Ca^2＋ concentration can switch the cellular behavior from proliferation to terminal differentiation or quiescence. As cancer remains predominantly a disease of disordered balance between proliferation, termination and apoptosis, disruption in the function of the Ca^2＋-sensing receptor may contribute to the progression of neoplastic disease. Loss of the growth suppressing effects of elevated extracellular Ca^2＋ have been demonstrated in colon carcinoma, and have been correlated with changes in the level of CaSR expression.

Altered physiology of gastrointestinal vagal afferents following neurotrauma

The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function.In both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically intact.However,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions.Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury.While the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal afferents.Since sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

Role of the microbiome in non-gastrointestinal cancers

"The forgotten organ",the human microbiome,comprises a community of microorganisms that colonizes various sites of the human body.Through coevolution of bacteria,archaea and fungi with the human host over thousands of years,a complex host-microbiome relationship emerged in which many functions,including metabolism and immune responses,became codependent.This coupling becomes evident when disruption in the microbiome composition,termed dysbiosis,is mirrored by the development of pathologies in the host.Among the most serious consequences of dysbiosis,is the development of cancer.As many as 20% of total cancers worldwide are caused by a microbial agent.To date,a vast majority of microbiomecancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers.Here,we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers,while distinguishing between viral and bacterial drivers of cancer,as well as "local" and "systemic","cancer-stimulating" and "cancer-suppressing" effects of the microbiome.Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis,and may enable to employ microbiome-targeting approaches as part of cancer treatment.

Gastrointestinal microbiome and cholelithiasis:Prospect in the nervous system

Dan and colleagues recently published research suggesting that the gastrointestinal microbiome(microorganisms and metabolites)in cholelithiasis.They reviewed gallbladder stones,choledocholithiasis,and asymptomatic gallstones.Finally,their discussion was on the gastrointestinal.We focused on complementing the effect of the S1 protein and neuroinflammatory changes caused by severe acute respiratory syndrome coronavirus 2.Our contribution was about to involve the microbiota and the nervous system.They can have similar functions because they have similar pathways and advantages,bearing in mindγ-aminobutyric acid in schizophrenia and serotonin in Parkinson's disease.Therefore in the next few years,more research should be encouraged on the microbiota consequences for development,and mobility.

Effect of microbiome group on immune checkpoint inhibitors in treatment of gastrointestinal tumors

In recent years,immune checkpoint blockade(ICB)therapy has become an important treatment strategy for gastrointestinal tumors,however,it only benefits about 1/3 of patients.Since the microbiome has been shown to play an important role in the human body for a long time,a growing number of studies are focusing on its relationship to ICB therapy in cancer,specifically how intestinal microbes affect the efficacy of immune checkpoint inhibitors(ICIs)therapy in patients.On this basis,probiotic interventions,fecal microbiota transplantation(FMT),dietary interventions,and other methods which improve or maintain the structure of the intestinal flora have attracted widespread attention.This article discusses the four aspects of the microbiome,ICB,combined treatment of gastrointestinal tumors,and regulation of gut microbiome.Particularly,the discussion focuses on the contribution of probiotic intervention in improving the therapeutic effect of ICIs to prolong the survival time of patients and reduce the severity of immune-related adverse effects(irAEs).

Gastrointestinal microbiome and primary Sjogren’s syndrome: a review of the literature and conclusions

The recognition of the profound impact of the human gastrointestinal microbiome(GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjogren’s syndrome(pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with p SS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and p SS,with the aim of contributing to future research and to the development of new clinical applications.

Gastrointestinal Microbiome and related metabolites in Depression and Antidepressants - a comprehensive review

Depression,a prevalent mood disorder,has emerged as a significant health concern in society.While the exact cause of depression remains incompletely understood,there is substantial evidence linking the gastrointestinal microbiome and its metabolites to this condition.Through combined multi-omics analysis,it has been observed that the composition of the gastrointestinal microbiome,including Firmicutes,Bacteroidetes,and Actinobacteria,undergoes significant alterations in depressed individuals.Moreover,the production of short-chain fatty acids,tryptophan,and bile acids by these gut microbes is also found to be modified in depression.Furthermore,studies have demonstrated that antidepressant medications exert their therapeutic effects by interacting with the gastrointestinal microbiome and their metabolites.This review provides an overview of the association between the gastrointestinal microbiome,related metabolites,and depression.It highlights the potential of these factors to serve as mechanisms of action for antidepressant medications.Additionally,the review summarizes the commonly used technical tools in depression research.

Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

Application of zebrafish in the study of the gut microbiome

Zebrafish(D anio rerio)have attracted much attention over the past decade as a reliable model for gut microbiome research.Owing to their low cost,strong genetic and development coherence,efficient preparation of germ-f ree(GF)larvae,availability in high-t hroughput chemical screening,and fitness for intravital imaging in vivo,zebrafish have been extensively used to investigate microbiome-h ost interactions and evaluate the toxicity of environmental pollutants.In this review,the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm-b looded animal models are first summarized.Then,the roles of zebrafish gut microbiome on host development,metabolic pathways,gut-b rain axis,and immune disorders and responses are addressed.Furthermore,their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed.We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification,resistance against bacterial infection,and disease prevention and cure.Overall,the zebrafish model promises a brighter future for gut microbiome research.

Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant(estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats(n = 23) were randomly divided into(1) non-pregnant,(contractility, n =6; transit, n = 6); and(2) pregnant(contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry(ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions(3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying(168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control(54.23 ± 15.14 ng/m L and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0(44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.

Gut microbiota in gastrointestinal diseases during pregnancy

Gut microbiota(GM)is a micro-ecosystem composed of all microorganisms in the human intestine.The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host.Dysbiosis of the GM may cause various diseases.GM has been demonstrated to be associated with human health and disease,and changes during individual development and disease.Pregnancy is a complicated physiological process.Hormones,the immune system,metabolism,and GM undergo drastic changes during pregnancy.Gastrointestinal diseases during pregnancy,such as hepatitis,intrahepatic cholestasis of pregnancy,and pre-eclampsia,can affect both maternal and fetal health.The dysregulation of GM during pregnancy may lead to a variety of diseases,including gastrointestinal diseases.Herein,we review recent research articles on GM in pregnancy-related gastrointestinal diseases,discuss the interaction of the GM with the host under normal physiological conditions,gastrointestinal diseases,and pregnancy-specific disorders.As more attention is paid to reproductive health,the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.

COVID-19 and the gastrointestinal tract:Source of infection or merely a target of the inflammatory process following SARS-CoV-2 infection?

Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)patients.This clinical evidence is supported by the detection of viral RNA in stool,which also supports the hypothesis of a possible fecal-oral transmission route.The involvement of GI tract in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2,which is a SARS-CoV-2 target receptor,is present along the GI tract.Studies have pointed out that gut dysbiosis may occur in COVID-19 patients,with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children.However,the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection.In such a scenario,pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients.Considering the possibility of a fecal-oral transmission route,water and environmental sanitation play a crucial role for COVID-19 containment,especially in developing countries.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

Risk factors and their interactive effects on severe acute pancreatitis complicated with acute gastrointestinal injury

BACKGROUND There are many risk factors for severe acute pancreatitis(SAP)complicated with acute gastrointestinal injury(AGI),but few reports on the interaction between these risk factors.AIM To analyze the risk factors for SAP complicated with AGI and their interactive effects.METHODS We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022.They were divided into AGI group and non-AGI group according to whether AGI was present.Demographic data and laboratory test data were compared between the two groups.The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression,and an analysis of the interaction of the risk factors was performed.RESULTS The percentage of patients with multiple organ dysfunction syndrome,acute physiological and chronic health scoring system II(APACHE II)score,white blood cell count and creatinine(CRE)level was higher in the AGI group than in the non-AGI group.There was a statistically significant difference between the two groups(P<0.05).Logistic regression analysis indicated that an APACHE II score>15 and CRE>100μmol/L were risk factors for SAP complicating AGI.The interaction index of APACHE II score and CRE level was 3.123.CONCLUSION An APACHE II score>15 and CRE level>100μmol/L are independent risk factors for SAP complicated with AGI,and there is a positive interaction between them.

Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients

Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a major global public health event,resulting in a significant social and economic burden.Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection,recent evidence suggests that it is a complex disease including gastrointestinal symptoms,such as diarrhea,nausea,and vomiting.Moreover,it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms.This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier,chemical barrier,microbial barrier,and immune barrier.

Clinical relevance of intestinal barrier dysfunction in common gastrointestinal diseases

The intestinal barrier is a complex and well-controlled physiological construct designed to separate luminal contents from the bowel wall.In this review,we focus on the intestinal barrier’s relationship with the host’s immune system interaction and the external environment,specifically the microbiome.The bowel allows the host to obtain nutrients vital to survival while protecting itself from harmful pathogens,luminal antigens,or other pro-inflammatory factors.Control over barrier function and the luminal milieu is maintained at the biochemical,cellular,and immunological level.However,disruption to this highly regulated environment can cause disease.Recent advances to the field have progressed the mechanistic understanding of compromised intestinal barrier function in the context of gastrointestinal pathology.There are numerous examples where bowel barrier dysfunction and the resulting interaction between the microbiome and the immune system has disease-triggering consequences.The purpose of this review is to summarize the clinical relevance of intestinal barrier dysfunction in common gastrointestinal and related diseases.This may help highlight the importance of restoring barrier function as a therapeutic mechanism of action in gastrointestinal pathology.

Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review

By its nature, Gulf war illness(GWI) is multi-symptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation,pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war(GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies,which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 phase.Long CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental models.Here,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long CovID.We highlight the potential mechanisms and possible treatment based on Gl health and microbiome.Finally,we discuss challenges and future direction in the long CoVID clinic and research.