Metabolomics profile in gastrointestinal cancers:Update and future perspectives

Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.

Microbiota shaping — the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review

BACKGROUND Dementia is a chronic progressive neurological disease affecting millions of people worldwide,and represents a relevant economic burden for healthcare systems.Although its pathogenesis is still unknown,recent findings have reported that a dysregulated gut-brain axis communication,a fundamental relationship mediated by several host and microbial molecules,is associated with cognitive disorders.In addition,gut microbiota manipulation reduces neuroinflammation,improving cognitive function by restoring the functional gut-brain axis.AIM To better define the effects of probiotics,prebiotics,synbiotics,and fecal microbiota transplant(FMT)on cognitive function.METHODS We performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics,prebiotics,synbiotics,or FMT on cognition outcomes in healthy or sick people of every age,sex,and nationality.We systematically searched Embase,Medline/PubMed,Cochrane Library,central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation.Then we carefully reviewed and synthesized the data by type of study design and setting,characteristics of the studied population,kind of intervention(strain type or mixture type,dosage,and frequency of administration),control treatment,inclusion and exclusion criteria,follow-up duration,and cognitive or memory outcomes.RESULTS After examining the titles and abstracts,the initial literature screening identified 995 articles,but we added 23 papers in our systematic review.The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires.We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests.Regarding unhealthy subjects,while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions,supplementation with prebiotics did not provide any cognitive improvement.CONCLUSION Probiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.

Effect of ancient Khorasan wheat on gut microbiota,inflammation,and short-chain fatty acid production in patients with fibromyalgia

BACKGROUND Fibromyalgia(FM)syndrome is mainly characterized by widespread pain,sleeping disorders,fatigue,and cognitive dysfunction.In many cases,gastrointestinal distress is also reported,suggesting the potential pathogenic role of the gut microbiota(GM).The GM is deeply influenced by several environmental factors,especially the diet,and recent findings highlighted significant symptom improvement in FM patients following various nutritional interventions such as vegetarian diet,low-fermentable oligosaccharides,disaccharides,monosaccharides,and polyols based diets,gluten-free diet,and especially an ancient grain supplementation.In particular,a recent study reported that a replacement diet with ancient Khorasan wheat led to an overall improvement in symptom severity of FM patients.AIM To examine the effects of ancient Khorasan wheat on the GM,inflammation,and short-chain fatty acid production in FM patients.METHODS After a 2-wk run-in period,20 FM patients were enrolled in this randomized,double-blind crossover trial.In detail,they were assigned to consume either Khorasan or control wheat products for 8 wk and then,following an 8-wk washout period,crossed.Before and after treatments,GM characterization was performed by 16S rRNA sequencing while the fecal molecular inflammatory response and the short-chain fatty acids(SCFAs)were respectively determined with the Luminex MAGPIX detection system and a mass chromatography-mass spectrometry method.RESULTS The Khorasan wheat replacement diet,in comparison with the control wheat diet,had more positive effects on intestinal microbiota composition and on both the fecal immune and SCFAs profiles such as the significant increase of butyric acid levels(P=0.054),candidatus Saccharibacteria(P=9.95e-06)and Actinobacteria,and the reduction of Enterococcaceae(P=4.97e-04).Moreover,the improvement of various FM symptoms along with the variation of some gut bacteria after the Khorasan wheat diet have been documented;in fact we reported positive correlations between Actinobacteria and both Tiredness Symptoms Scale(P<0.001)and Functional Outcome of Sleep Questionnaire(P<0.05)scores,between Verrucomicrobiae and both Widespread Pain Index(WPI)+Symptom Severity scale(SS)(P<0.05)and WPI(P<0.05)scores,between candidatus Saccharibacteria and SS score(P<0.05),and between Bacteroidales and Sleep-Related and Safety Behaviour Questionnaire score(P<0.05).CONCLUSION The replacement diet based on ancient Khorasan wheat results in beneficial GM compositional and functional modifications that positively correlate with an improvement of FM symptomatology.

Exploring the food-gut axis in immunotherapy response of cancer patients

Nowadays,immunotherapy is widely used to treat different cancer types as it boosts the body's natural defenses against the malignancy,with lower risk of adverse events compared to the traditional treatments.The immune system is able to control cancer growth but,unfortunately,many cancers take advantage of immune checkpoints pathways for the immune evasion.An intricate network of factors including tumor,host and environmental variables influence the individual response to immune checkpoints’inhibitors.Between them,the gut microbiota(GM)has recently gained increasing attention because of its emerging role as a modulator of the immune response.Several studies analyzed the diversities between immunotherapy-sensitive and immunotherapy-resistant cohorts,evidencing that particular GM profiles were closely associated to treatment effect.In addition,other data documented that interventional GM modulation could effectively enhance efficacy and relieve resistance during immunotherapy treatment.Diet represents one of the major GM determinants,and ongoing studies are examining the role of the food-gut axis in immunotherapy treatment.Here,we review recent studies that described how variations of the GM affects patient’s responsivity to anti-cancer immunotherapy and how diet-related factors impact on the GM modulation in cancer,outlining potential future clinical directions of these recent findings.

Impact of microbiota-immunity axis in pancreatic cancer management

The microbiota impact on human diseases is well-known,and a growing body of literature is providing evidence about the complex interplay between microbiotaimmune system-human physiology/pathology,including cancers.Together with the defined risk factors(e.g.,smoke habits,diet,diabetes,and obesity),the oral,gut,biliary,and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system.Unfortunately,a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured.Given the poor pancreatic cancer prognosis,complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential noninvasive biomarkers,new therapeutic targets,and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.

Molecular methods for colorectal cancer screening:Progress with next-generation sequencing evolution

Currently,colorectal cancer(CRC)represents the third most common malignancy and the second most deadly cancer worldwide,with a higher incidence in developed countries.Like other solid tumors,CRC is a heterogeneous genomic disease in which various alterations,such as point mutations,genomic rearrangements,gene fusions or chromosomal copy number alterations,can contribute to the disease development.However,because of its orderly natural history,easily accessible onset location and high lifetime incidence,CRC is ideally suited for preventive intervention,but the many screening efforts of the last decades have been compromised by performance limitations and low penetrance of the standard screening tools.The advent of next-generation sequencing(NGS)has both facilitated the identification of previously unrecognized CRC features such as its relationship with gut microbial pathogens and revolutionized the speed and throughput of cataloguing CRC-related genomic alterations.Hence,in this review,we summarized the several diagnostic tools used for CRC screening in the past and the present,focusing on recent NGS approaches and their revolutionary role in the identification of novel genomic CRC characteristics,the advancement of understanding the CRC carcinogenesis and the screening of clinically actionable targets for personalized medicine.

Gut microbiota and immune system in liver cancer:Promising therapeutic implication from development to treatment

Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.

Potential therapeutic strategies to target gut microbiota in hepatocellular carcinoma

The gut microbiota(GM)is an assorted ecosystem,composed of viruses,fungi,protozoa,archaea,and especiallybacteria,which exist in a definite symbiosis betweeneach other and the host(human)as well.Increasing datadocument that GM plays key parts in human physiology,taking part in the digestive process,vitamin B synthesis,promotion of angiogenesis and nerve functionality,andnotably in the maturation and modulation of the immunesystem.