Impact Of Gut Microbiome Research Articles

The impact of gut microbiome on neuro-autoimmune demyelinating diseases

The impact of gut microbiome on neuro-autoimmune demyelinating diseases

The Impact of Gut Microbiome on Prostate Health and BPH Progression: A Comprehensive Review

The Impact of Gut Microbiome on Prostate Health and BPH Progression: A Comprehensive Review

Impact of Gut Microbiome and Diet on Post-acute Sequelae of COVID-19 Syndrome (PASC) (P11-13.007)

Impact of Gut Microbiome and Diet on Post-acute Sequelae of COVID-19 Syndrome (PASC) (P11-13.007)

Etiology, Epidemiology, and Therapeutic Approaches for Primary Sclerosing Cholangitis in the Context of Concurrent Non-specific Inflammatory Bowel Diseases

Introduction: Primary sclerosing cholangitis (PSC) is a chronic, idiopathic disease characterized by persistent and progressive inflammation of the intrahepatic and/or extrahepatic bile ducts. This leads to fibrosis, cholestatic complications, and liver failure. In over 70% of patients, non-specific intestinal inflammations coexist, particularly ulcerative colitis, and sporadically Crohn's disease. Aim: Our study aimed to assess current literature on primary sclerosing cholangitis (PSC), covering its causes, symptoms, treatment methods, and the connection between PSC and inflammatory bowel disease (IBD) co-occurrence. Materials and methods: We conducted a PubMed literature review using keywords like "primary sclerosing cholangitis pathogenesis," "primary sclerosing cholangitis and inflammatory bowel disease," and "primary sclerosing cholangitis and ulcerative colitis.” Results: Our research extensively covered PSC epidemiology, pathogenesis, and treatment options. Emphasis was placed on the heightened prevalence of inflammatory bowel diseases, including ulcerative colitis, among PSC patients. Summary: Primary sclerosing cholangitis (PSC) is a disease causing gradual damage to bile ducts within or outside the liver. Over 70% of patients also experience inflammatory bowel disease (IBD), mainly ulcerative colitis. The exact causes of PSC and its connection to IBD remain unclear. The theories involve hyperactive "intestinal" T cells or the impact of gut microbiome on their growth. Presently, a liver transplant stands as the sole remedy.

The gut microbiome modulates associations between adherence to a Mediterranean-style diet, abdominal adiposity, and C-reactive protein in population-level analysis

BackgroundAdherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. ObjectivesTo examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. DesignIn a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP). ResultsHigher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; β: −20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively. ConclusionThese novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation.

Gut Phageome-An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases.

The gut microbiota, including bacteria, archaea, fungi, and viruses, compose a diverse mammalian gut environment and are highly associated with host health. Bacteriophages, the viruses that infect bacteria, are the primary members of the gastrointestinal virome, known as the phageome. However, our knowledge regarding the gut phageome remains poorly understood. In this review, the critical role of the gut phageome and its correlation with mammalian health were summarized. First, an overall profile of phages across the gastrointestinal tract and their dynamic roles in shaping the surrounding microorganisms was elucidated. Further, the impacts of the gut phageome on gastrointestinal fitness and the bacterial community were highlighted, together with the influence of diets on the gut phageome composition. Additionally, new reports on the role of the gut phageome in the association of mammalian health and diseases were reviewed. Finally, a comprehensive update regarding the advanced phage benchwork and contributions of phage-based therapy to prevent/treat mammalian diseases was provided. This study provides insights into the role and impact of the gut phagenome in gut environments closely related to mammal health and diseases. The findings provoke the potential applications of phage-based diagnosis and therapy in clinical and agricultural fields. Future research is needed to uncover the underlying mechanism of phage-bacterial interactions in gut environments and explore the maintenance of mammalian health via phage-regulated gut microbiota.

Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights.

The gut microbiome plays an important role in the variation of pharmacologic response. This aspect is especially important in the era of precision medicine, where understanding how and to what extent the gut microbiome interacts with drugs and their actions will be key to individualizing therapy. The impact of the composition of the gut microbiome on the efficacy of newer cancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell treatment has become an active area of research. Pancreatic adenocarcinoma (PAC) has a poor prognosis even in those with potentially resectable disease, and treatment options are very limited. Newer studies have concluded that there is a synergistic effect for immunotherapy in combination with cytotoxic drugs, in the treatment of PAC. A variety of commensal microbiota can affect the efficacy of conventional chemotherapy and immunotherapy by modulating the tumor microenvironment in the treatment of PAC. This review will provide newer insights on the impact that alterations made in the gut microbial system have in the development and treatment of PAC.

Impact of gut microbiome on the renin-aldosterone system: Shika-machi Super Preventive Health Examination results.

The renin-angiotensin-aldosterone system (RAAS) is a regulatory mechanism of the endocrine system and is associated with various diseases, including hypertension and renal and cardiovascular diseases. The gut microbiota (GM) have been associated with various diseases, mainly in animal models. However, to our knowledge, no studies have examined the relationship between the RAAS and GM in humans. The present study aimed to assess the association between the systemic RAAS and GM genera and their causal relationships. The study participants were 377 members of the general population aged 40 years or older in Shika-machi, Japan. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), and GM composition were analyzed using the 16S rRNA method. The participants were divided into high and low groups according to the PRA, PAC, and ARR values. U-tests, one-way analysis of covariance, and linear discriminant analysis of effect size were used to identify the important bacterial genera between the two groups, and binary classification modeling using Random Forest was used to calculate the importance of the features. The results showed that Blautia, Bacteroides, Akkermansia, and Bifidobacterium were associated with the RAAS parameters. Causal inference analysis using the linear non-Gaussian acyclic model revealed a causal effect of Blautia on PAC via SBP. These results strengthen the association between the systemic RAAS and GM in humans, and interventions targeting the GM may provide new preventive measures and treatments for hypertension and renal disease.

Impact of gut microbiome on serum IgG4 levels in the general population: Shika-machi super preventive health examination results.

Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system. IgG4-related diseases (IgG4-RD) are intractable diseases in which IgG4 levels in the blood are elevated, causing inflammation in organs such as the liver, pancreas, and salivary glands. IgG4-RD are known to be more prevalent in males than in females, but the etiology remains to be elucidated. This study was conducted to investigate the relationship between gut microbiota (GM) and serum IgG4 levels in the general population. In this study, the relationship between IgG4 levels and GM evaluated in male and female groups of the general population using causal inference. The study included 191 men and 207 women aged 40 years or older from Shika-machi, Ishikawa. GM DNA was analyzed for the 16S rRNA gene sequence using next-generation sequencing. Participants were bifurcated into high and low IgG4 groups, depending on median serum IgG4 levels. ANCOVA, Tukey's HSD, linear discriminant analysis effect size, least absolute shrinkage and selection operator logistic regression model, and correlation analysis revealed that Anaerostipes, Lachnospiraceae, Megasphaera, and [Eubacterium] hallii group were associated with IgG4 levels in women, while Megasphaera, [Eubacterium] hallii group, Faecalibacterium, Ruminococcus.1, and Romboutsia were associated with IgG4 levels in men. Linear non-Gaussian acyclic model indicated three genera, Megasphaera, [Eubacterium] hallii group, and Anaerostipes, and showed a presumed causal association with IgG4 levels in women. This differential impact of the GM on IgG4 levels based on sex is a novel and intriguing finding.

Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference.

Dyslipidemia (DL) is one of the most common lifestyle-related diseases. There are few reports showing the causal relationship between gut microbiota (GM) and DL. In the present study, we used a linear non-Gaussian acyclic model (LiNGAM) to evaluate the causal relationship between GM and DL. A total of 79 men and 82 women aged 40 years or older living in Shika-machi, Ishikawa Prefecture, Japan were included in the analysis, and their clinical information was investigated. DNA extracted from the GM was processed to sequence the 16S rRNA gene using next-generation sequencing. Participants were divided into four groups based on sex and lipid profile information. The results of one-way analysis of covariance, linear discriminant analysis effect size, and least absolute value reduction and selection operator logistic regression model indicated that several bacteria between men and women may be associated with DL. The LiNGAM showed a presumed causal relationship between different bacteria and lipid profiles in men and women. In men, Prevotella 9 and Bacteroides were shown to be potentially associated with changes in low- and high-density lipoprotein cholesterol levels. In women, the LiNGAM results showed two bacteria, Akkermansia and Escherichia/Shigella, had a presumptive causal relationship with lipid profiles. These results may provide a new sex-based strategy to reduce the risk of developing DL and to treat DL through the regulation of the intestinal environment using specific GM.

The Impact of Gut Microbiome on Maternal Fructose Intake-Induced Developmental Programming of Adult Disease.

Excessive or insufficient maternal nutrition can influence fetal development and the susceptibility of offspring to adult disease. As eating a fructose-rich diet is becoming more common, the effects of maternal fructose intake on offspring health is of increasing relevance. The gut is required to process fructose, and a high-fructose diet can alter the gut microbiome, resulting in gut dysbiosis and metabolic disorders. Current evidence from animal models has revealed that maternal fructose consumption causes various components of metabolic syndrome in adult offspring, while little is known about how gut microbiome is implicated in fructose-induced developmental programming and the consequential risks for developing chronic disease in offspring. This review will first summarize the current evidence supporting the link between fructose and developmental programming of adult diseases. This will be followed by presenting how gut microbiota links to common mechanisms underlying fructose-induced developmental programming. We also provide an overview of the reprogramming effects of gut microbiota-targeted therapy on fructose-induced developmental programming and how this approach may prevent adult-onset disease. Using gut microbiota-targeted therapy to prevent maternal fructose diet-induced developmental programming, we have the potential to mitigate the global burden of fructose-related disorders.

Surveillance utilizes multi-omics in cardiovascular disease: Diet and its potentiality in Preventive index

Cardiovascular Disease (CVD) is characterized by multidimensional risks including drug, diet, lifestyle, stress, and metabolomics diseases which cause mortality and morbidity depending on age and status of chronic diseases. However, emerging evidence indicated it is preventable health complications that depend on risk management along with lifestyle change, and personalized medication that include alternative measures like Diet use following molecular diagnostic and imaging analysis. CVD is mainly attributed to the narrowing of blood vessels through atherosclerotic lesions and/or thrombosis. Hypertension, obesity, and hyperlipidemia are major risk factors for the development of CVD and treating these diseases is essential in slowing down progression of CVD. Inflammation appears to play a pivotal role in CVD and can be measured through a simple blood assay (CRP). Multi-omics approaches have been essential in the development of treatments for CVD, in the prevention of CVD, and in the diagnosis of CVD. There are many outcomes available to help with diagnosing CVD and omics platforms have helped scientists and clinician develop these diagnostic tools. Radiomics has played a key part in the diagnosis of CVD as being able to view the diseased heart is essential in determining CVD progression and the treatment options suitable for that secondary disease related. Nutrigenomics is emerging as the future of medicine such as utilizing treatment strategy innovation instead of medications, but it is still in its infancy. Nutrigenomics will open the doors to different therapeutic drug targets and allow us the ability to be more specific in our treatment options. There are only a few gene-diet interactions documented that increase a person’s chances of developing CVD. Curating an individual diet and treatment plan based on somebody’s genetic disposition or skewed immune responses following personalized diagnosis will be essential in the survival of these severe CVD patients. Key issues referring to risk surveillance and prevention is a distant approach which reflects several factors: for example, what type of tools can be used to conduct diagnosis, molecular diagnostic tools detect what type of biomarkers are present prior to prescribing the personalized diet and to ensure diagnostic accuracy. Recently, increasing findings emphasize dual aspects of diet such as immune enhancers and modulators in which gut microbiota has been proven to play a major factor in development of CVD. The future direction of omics studies will foster the ability to test the impact of gut microbiome of a patient with CVD following diet driven organ protection as well as prescribe essential components of the diet that can be adjusted with proper probiotic medication. Proper diet adjustments can correct the organ dysfunction that occurred due to interaction between molecular mismatch and cellular damage following stress-mediated damage or chronic disease. Further micro-scale assays and molecular diagnostic techniques following nutrigenomics application to the patient could be beneficial to allow patient’ care shift from physician driven and clinic based to self-management with knowledge based at home treatment programs that work by envisioning molecular reprogramming and rejuvenation of damaged organ. These at home treatments can be utilized with development of radiological data with innovation of software. The aim of the short review is to visualize the current role of nutrigenomics and diet formulation for integrative care (e.g., diagnosis, prevention, and treatment of CVD) which would take advantage of earlier prevention synchronized with current medical tests, imaging techniques. Health economy like management can reduce medical cost with disease prevention disease and could modulate the following: enhance knowledge-based interaction between body and diet, discuss cognitive enhancement how sensing with molecular behavior under image-management platform, monitor drug surveillance of current treatment options in CVD and the pitfalls of current omics application and data transformation needs for patient care in the future.

The impact of gut microbiome in Parkinson's disease

Most patients diagnosed with PD show gastrointestinal symptoms as one of the earliest features. For example, PD patients often complain of gastrointestinal distress such as constipation and nausea. It is important to note that about 60% of PD patients suffer from constipation, which can begin 20 years before diagnosis and is one of the prodromal syndromes.

The impact of gut microbial composition on response to neoadjuvant chemotherapy (NACT) in early-stage triple negative breast cancer (TNBC).

590 Background: The impact of gut microbiome on tumor biology, progression and response to immunotherapy has been shown across cancer types. However, there is little known about the impact of gut microbial composition on response to chemotherapy. We have previously shown that the gut microbiome remains unaltered during NACT in a cohort of 32 patients. Here we investigate the association between gut microbiome and response to NACT in a larger cohort of early-stage TNBC. Methods: Longitudinal fecal samples were collected from 85 patients with newly-diagnosed, early-stage TNBC patients enrolled in the ARTEMIS trial (NCT02276443). Patients all received standard NACT with adriamycin/cyclophosphamide (AC); volumetric change was assessed using ultrasound and patients with < 70% volumetric reduction (VR) after 4 cycles of AC were recommended to receive targeted therapy in addition to standard NACT to improve response rates. We performed 16S sequencing on bacterial genomic DNA extracted from 85 pre-AC fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 138. For differential taxa-based univariate analysis, abundant microbiome taxa at species, genus, family, class, and order levels were analyzed using DESeq2 after logit transformation. Alpha-diversity indices within group categories were calculated using phyloseq. Microbial alpha diversity (within-sample diversity) was measured by Simpson's reciprocal index. β-diversity was measured using weighted UniFrac distances between the groups. The association between microbiota abundance and pathologic complete response (pCR) or residual disease (RD) was assessed using DESeq2 analysis. Results: Pre-AC fecal samples from 85 patients were available for analysis. Amongst them, there were 46 patients with pCR and 39 patients with RD. There was no significant difference in alpha diversity (p = 0.8) or beta-diversity (p = 0.7) between the pCR and RD groups. However, relative to patients with RD, the gut microbiome in patients with pCR was enriched for the Bifidobacterium longum species (p = 0.03). The gut microbiome in patients with RD was enriched for Lachnospiraceae (p = 0.03) at the genus level and the Bacteroides thetaiotaomicron species (p = 0.02). Conclusions: We have demonstrated significant differences in the gut microbial composition in patients with pCR as compared to patients with RD. Further investigation in larger studies is needed to support therapeutic exploration of gut microbiome modulation in TNBC patients receiving chemotherapy such as probiotic supplementation or fecal microbiota transplant.

The Impact of Gut Microbiome on Metabolic Disorders During Catch-Up Growth in Small-for-Gestational-Age.

ObjectiveCatch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.MethodsAn SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.ResultsThe composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria.Conclusion Lactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.

The Impact of Gut Microbiome on the Pharmacokinetics of Ginsenosides Rd and Rg3 in Mice after Oral Administration of Red Ginseng.

Ginsenosides of orally administered red ginseng (RG) extracts are metabolized and absorbed into blood. Here, we examined the pharmacokinetic profiles of ginsenosides Rd and Rg3 in mice orally gavaged with RG, then investigated the correlations between these and gut microbiota composition. RG water extract (RGw), RG ethanol extract (RGe), or fermented RGe (fRGe) was orally gavaged in mice. The plasma concentrations of the ginsenosides were determined, and the gut microbiota composition was analyzed. RGe and fRGe-treated mice showed higher plasma concentration levels of ginsenoside Rd compared with RGw-treated mice; particularly, ginsenoside Rd absorbed was substantially high in fRGe-treated mice. Oral administration of RG extracts modified the gut microbiota composition; the modified gut microbiota, such as Peptococcaceae, Rikenellaceae, and Hungateiclostridiaceae, were closely correlated with the absorption of ginsenosides, such as Rd and Rg3. These results suggest that oral administration of RG extracts can modify gut microbiome, which may consequently affect the bioavailability of RG ginsenosides.

43 Feed efficiency and behavior are associated with gut microbiome in three breeds of pigs

Abstract Feed efficiency and behavior are important traits in the pork industry for economic, welfare, and environmental aspects. The gut microbiota plays an important role in nutrient digestibility and it is likely to influence these traits. The aim of this study was to characterize the feed efficiency, feeding behavior and gut microbiome relationships of pigs belonging to three different breeds. Individual body weight, feed intake and rate of Duroc (n = 222), Landrace (n = 244), and Large White (n = 221) pigs were recorded. Rectal fecal samples were collected from each animal at three time points (T1, start of trial; T2, mid-trial; T3, end of trial) and used for microbiome 16S rRNA gene sequencing. Individual feed intake and body weight were edited to obtain average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio (FCR), average daily feeding rate (ADFR), average feed intake per visit (AFIV), average daily number of visits to feeder (ANVD), average daily occupation time (AOTD), average occupation time per visit (AOTV). The impact of gut microbiome on the traits studied was present and seemed to depend on the breed and the time point of recording. At T1, Oscillibacter and Phascolarctobacterium had negative impact on ANVD and ADFI in Duroc, Ruminococcus had negative impact on ADFI in Landrace and Parvimonas, Escherichia and Anaerovibrio had negative impact on ADFI and ANVD in Large White. At T2, Lactobacillus showed a positive impact on ADFR in Landrace and on ADFI in Large White. At T3, Ruminococcus, Faecalibacterium and Dorea had a positive impact on ADFI in Duroc, Staphylococcous had positive impact on ADFR in Landrace and Peptoniphilus had negative impact on ADFI in Large White. Gut microbiome may have an heterogenous impact on the regulation of feeding behavior and feed efficiency depending on the host genotype.

Impact of Gut Microbiome on Hypertensive Patients With Low-Salt Intake: Shika Study Results.

Salt intake is one of the most important environmental factors impacting hypertension onset. Meanwhile, the potential roles of the gut microbiome (GM) in altering the health status of hosts have drawn considerable attention. Here, we aimed to perform an observational study to investigate the impact of intestinal bacterial flora in hypertensive patients with low-salt or high-salt intake. A total of 239 participants were enrolled, and their gut microbiomes, clinical and demographic details, as well as physiological parameters pertaining to the renin-angiotensin-aldosterone system and inflammatory cytokine profiles, were examined. The participants were classified into four groups based on the presence of different enterotype bacteria, as determined via cluster analysis, and salt intake: low salt/GM enterotype 1, low salt/GM enterotype 2, high salt/GM enterotype 1, and high salt/GM enterotype 2. Results show that the prevalence of hypertension was significantly lower in the low-salt/GM enterotype 2 group (27%) compared to the low salt/GM enterotype 1 group (47%; p = 0.04). Alternatively, no significant differences were observed in hypertension prevalence between the two high-salt intake groups (GM enterotype 1 = 50%, GM enterotype 2 = 47%; p = 0.83). Furthermore, The low-salt/GM enterotype 2 was higher in the relative abundances of Blautia, Bifidobacterium, Escherichia-Shigella, Lachnoclostridium, and Clostridium sensu stricto than the low-salt/GM enterotype 1. differed significantly between the GM enterotypes. These results suggested that consumption of a low-salt diet was ineffective in regulating hypertension in individuals with a specific gut bacteria composition. Our findings support the restoration of GM homeostasis as a new strategy for controlling blood pressure and preventing the development of hypertension.

Abstract 4960: Studying the impact of gut microbiome to hepatocellular cancer in an orthotopic murine model

Abstract Background and Objective: As one of the most important components of human body, gut microbiota play a vital role in human health by participating in metabolomics and maintaining immunological homeostasis. Microbiota dysbiosis is significantly associated with initiation and progression of different diseases. Due to close anatomical and functional connection between gut and liver (gut-liver axis), gut microbiota are found to impact the development of liver diseases including hepatocellular cancer (HCC) without fully understanding mechanisms. The overall objective of present study is to investigate how microbiota modulate HCC growth by regulating intrahepatic immune response. Methods: Administration of carbon tetrachloride in combination with transplant of oncogenic hepatocytes by intrasplenic injection was used to make an orthotopic mouse model of HCC. A specific antibiotics cocktail (ABX) was selected to inhibit some kinds of gut microbiota. 16s rRNA sequencing was used to characterize gut microbiota profile in mice with the different treatments. Magnetic resonance imaging (MRI) was used to monitor tumor growth. Adoptive transfer of tumor antigen-specific CD8+ T cells following the treatment was used to investigate how ABX administration impacted intrahepatic immune response. Flow cytometry and multiplex cytokine assay were used to detect the alteration of effector CD8+ T cell in phenotype, proliferation, and function. Immunohistochemistry (IHC) was used to investigate immune cell tumor-infiltration. Results: The established murine model reflects the typical features of human HCC. ABX oral administration significantly changed gut microbiota composition, particularly in abundance of P. aeruginosa and Muribaculaceae. ABX-mediated alteration of gut microbiota significantly retarded HCC progression. Interestingly, ABX treatment was found to prevent adoptively transferred tumor antigen-specific CD8+ T cell from tumor-induced immune tolerance, as higher frequency of effector CD8+ T cell was detected in ABX-treated tumor-bearing mice compared to that in control tumor-bearing mice. Correspondingly, ABX treatment resulted in the increase in expression of CD69 and enhanced production of IFN-γ in tumor antigen-specific CD8+ T cells relevant to that in control mice. Conclusion: Modulating microbiota with antibiotics is able to shape intrahepatic immune responses and therapeutically suppress tumor growth, providing a new option in HCC control. Citation Format: Xiaoqiang Qi, Ming Yang, Joseph Stenberg, Guangfu Li, Kevin Staveley-O’Carroll. Studying the impact of gut microbiome to hepatocellular cancer in an orthotopic murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4960.

Role of microbiota function during early life on child's neurodevelopment

BackgroundThere are critical periods during pregnancy and early life when child's neurodevelopment can be altered, where different factors including hormones, stress, genetics, and diet have an important role. Novel studies are indicating that also gut microbiota and maternal obesity can influence child's neurodevelopment. Scope and approachThis review summarises the current concepts related to microbiota-gut-brain axis, including microbiota modulation of the eating behaviour, child's cognitive function and brain structure, microbiota analysis techniques and neurodevelopment assessment in children. Further, we propose and present knowledge about potential mechanisms of action and ways to intervene for disease prevention and treatments, opening up an exciting area with important medical and industrial applications. Key findings and conclusionsThis novel and fast developing research area is indicating that gut microbiota in association with body weight might have an important impact on foetal and child neurodevelopment. However, the exact mechanisms are not known and further research in the field is warranted. Within the MyNewGut Project we aim to analyse the impact of microbiota in association with body weight on cognitive and behaviour development in children. We will study the phylogeny and function of the gut microbial communities in overweight, obese and gestational diabetes pregnancies and in their progeny, in association with infants and children's cognitive and behavioural outcomes. As well, the impact of gut microbiome on brain structure and function during childhood will be evaluated. Results from this study will shed light on the impact of maternal and offspring gut microbiome and body weight on child's neurodevelopment, brain structure and function, and will suggest potential mechanisms for intervention.