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The first COVID-19 lockdown resulted in enforced quarantine of heavily affected areas with social isolation and related measures by several governments to slow the spread of the disease. The general population experienced several mental and lifestyle changes. Herein, we aimed to evaluate the metabolic and psychological effects induced by lifestyle changes during COVID-19 self-isolation among an Apulian overweight/obese cohort with metabolic disturbances. The study assessed anthropometric data (weight, abdominal circumferences), dietary habits (adherence to the Mediterranean diet, junk food score), lifestyle habits (i.e., smoking, and physical activity), levels of stress and anxiety, and depression. Subjects underwent bioumoral exams before and after self-isolation to monitor glycemic and lipid profiles. A total of 245 subjects (M:F = 118:127) have been included in the study. After lockdown, the number of obese subjects significantly increased in both sexes, and was higher in females than in males (P

It’s known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-hours ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and inverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-hour glucose ≥ 155 mg/dL (NGT ≥ 155) (36.4%) was higher than NGT

Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/β-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.

Massimo Bellini,1 Ginevra Berti,1 Leonilde Bonfrate,2 Flavia Ciranni,1 Agostino Di Ciaula,2 Mirko Di Ruscio,3 Alessandra Dell’Era,4,5 Christian Lambiase,1 Antonino Noto,2 Andrea Pancetti,1 Piero Portincasa,2 Francesco Rettura1 1Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 2Clinica Medica A. Murri, Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro Medical School, Bari, Italy; 3IBD Unit, IRCCS Ospedale Sacro Cuore-Don Calabria, Negrar di Valpolicella, Verona, Italy; 4Department of Biomedical and Clinical Sciences, “Luigi Sacco”, University of Milan, Milan, Italy; 5Gastroenterology and Endoscopy Unit – ASST Fatebenefratelli Sacco, Milan, ItalyCorrespondence: Francesco RetturaGastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyTel +39 50 997411Fax +39 50 997412Email rettura.fra@gmail.comAbstract: Irritable bowel syndrome is a chronic functional gastrointestinal disorder characterized by recurrent chronic abdominal pain and impaired bowel habits, which affects daily activity and work productivity, and is associated with a significant healthcare economic burden as well as an impaired quality of life and psycho-affective profile. Management of patients is a great challenge for physicians; at the present, the therapeutic strategy aimed to treat the different symptoms, and no medical therapy is proven to modify the natural history of the disease. GELSECTAN® (xyloglucan, pea protein and tannins, xylo-oligosaccharides) is a medical device with both protective and prebiotic actions on the intestinal mucosa, able to restore intestinal permeability and to improve gastrointestinal symptoms, controlling diarrhoea, abdominal pain and bloating in adult patients with irritable bowel syndrome. We report and discuss four cases of different patients with irritable bowel syndrome successfully managed with Gelsectan in the real clinical practice. Literature data, as well as these case reports, show that this device is effective and safe in improving symptoms and bowel habits associated to irritable bowel syndrome; its efficacy and safety were confirmed for the long-term use too. Agents with film-forming protective properties, such as Gelsectan, represent a new alternative therapeutic option for the management of patients with irritable bowel syndrome.Keywords: irritable bowel syndrome, GELSECTAN®, xyloglucan, tannins, xylo-oligosaccharides

In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known.We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). FibroScan® served to assess NAFLD by controlled attenuation parameter (CAP), and fibrosis by liver stiffness (LS). Patients with LS above 7 kPa were excluded. APRI and FIB-4 were used as additional serum biomarkers of fibrosis. The stable-isotope dynamic breath test was used to assess the hepatic efficiency of portal extraction (as DOBNAFLD occurred in 45%, 65.9%, and 91.3% of normal weight, overweight, and obese subjects, respectively. Biomarkers of liver fibrosis were comparable across subgroups, and LS was higher in obese, than in normal weight subjects. DOBOverweight, obesity and liver fat accumulation manifest with deranged portal extraction efficiency of methacetin into the steatotic hepatocyte. This functional alteration occurs early, and irrespective of significant fibrosis and presence of T2D.

Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide. Gut microbiota can play a role in the pathogenesis of NAFLD since dysbiosis is associated with reduced bacterial diversity, altered Firmicutes/Bacteroidetes ratio, a relative abundance of alcohol-producing bacteria, or other specific genera. Changes can promote disrupted intestinal barrier and hyperpermeability, filtration of bacterial products, activation of the immune system, and pro-inflammatory changes in the intestine, in the liver, and at a systemic level. Microbiota-derived molecules can contribute to the steatogenic effects. The link between gut dysbiosis and NAFLD, however, is confused by several factors which include age, BMI, comorbidities, dietary components, and lifestyle. The role of toxic chemicals in food and water requires further studies in both gut dysbiosis and NAFLD. We can anticipate that gut microbiota manipulation will represent a potential therapeutic tool to delay or reverse the progression of NAFLD, paving the way to primary prevention measures.

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.

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Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter 10 μm (PM

Background COVID‐19 is generating clinical challenges, lifestyle changes, economic consequences. The pandemic imposes to familiarize with concepts as prevention, vulnerability and resilience. Methods We analysed and reviewed the most relevant papers in the MEDLINE database on syndemic, noncommunicable diseases, pandemic, climate changes, pollution, resilience, vulnerability, health costs, COVID‐19. Results We discuss that comprehensive strategies must face multifactorial consequences since the pandemic becomes syndemic due to interactions with noncommunicable diseases, climate changes and iniquities. The lockdown experience, on the other hand, demonstrates that it is rapidly possible to reverse epidemiologic trends and to reduce pollution. The worst outcome is evident in eight highly industrialized nations, where 12% of the world population experienced about one‐third of all COVID‐19‐deaths worldwide. Thus, a great economic power has not been fully protective, and a change of policy is obviously needed to avoid irreversible consequences. Conclusions We are accumulating unhealthy populations living in unhealthy environments and generating unhealthy offspring. The winning policy should tackle structural inequities through a syndemic approach, to protect vulnerable populations from present and future harms.

The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. “Dynamic” liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope 13C. Hepatocellular metabolization of the substrate will generate 13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. 13C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, 13C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. 13C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of 13C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.

Background: COVID-19 patients frequently report residual symptoms after SARS-CoV-2 disappearance. However, the clinical post-COVID course of patients after mildly symptomatic COVID-19 is poorly known. We addressed this question because of our current clinical involvement in COVID-19 [1] and opening of a dedicated post-COVID19 outpatient clinic at 1, 3, 6, and 12 months after recovery. Materials and Methods: We enrolled 61 patients (26 males, age range 21-79 years) after a mild SARS-CoV-2 infection (i.e., no hospitalization, home quarantine, n = 48, or hospitalization to internal medicine/pneumology units for mild pneumonia, n = 13). The presence of 20 symptoms (dyspnea, fatigue, anxiety/depression, myalgia, memory impairment, chest pain, insomnia, joint pain, concentration impairment, cough, anosmia, headache, sicca syndrome, rhinitis, dysgeusia, alopecia, diarrhea, loss of appetite, dizziness, sweating, fever) was assessed semi-quantitatively by questionnaires before COVID-19, and 1 (n = 24), 3 (n = 29) or 6 months (n = 8 subjects) after recovery confirmed by two negative and consecutive nasopharyngeal swabs. Results: The prevalence of a cluster of six residual symptoms was higher after 1 month, than before infection: dyspnea (50% vs. 0%, respectively, P = 0.0001), fatigue (41.7% vs. 8.2%, p = 0.0002), myalgia (33.3% vs. 3.3%, p = 0.0001), memory impairment (33.3% vs. 13.1%, p = 0.03), insomnia (29.1% vs. 4.9%, p = 0.02), joint pain (25% vs. 8.2%, p = 0.03). The frequency of four of these symptoms was still higher after 3 months (dyspnea 24.5%, fatigue 58.6%, myalgia 31%, memory impairment 48.2% of cases;p < 0.03 in all cases vs. before infection). At this time, we observed an increased prevalence of concentration impairment (41.4% vs. 25% before infection, p = 0.001) and headache (24.1% vs. 6.6% before infection, p = 0.01). After 6 months all symptoms disappeared, except than fatigue (25%), memory impairment (12.5%) and headache (12.5%). Conclusions: A post-COVID syndrome occurs also in subjects with prior mild disease, and symptoms last 1-6 months after viral recovery. The prevalence of fatigue and neuropsychological symptoms, in particular, is still high after 6 months and should require support to improve public quality of life.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the hepatic expression of several metabolic abnormalities of high epidemiologic relevance. Fat accumulation in the hepatocytes results in cellular fragility and risk of progression toward necroinflammation, i.e., nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Several pathways contribute to fat accumulation and damage in the liver and can also involve the mitochondria, whose functional integrity is essential to maintain liver bioenergetics. In NAFLD/NASH, both structural and functional mitochondrial abnormalities occur and can involve mitochondrial electron transport chain, decreased mitochondrial β-oxidation of free fatty acids, excessive generation of reactive oxygen species, and lipid peroxidation. NASH is a major target of therapy, but there is no established single or combined treatment so far. Notably, translational and clinical studies point to mitochondria as future therapeutic targets in NAFLD since the prevention of mitochondrial damage could improve liver bioenergetics.

Obesity and non-alcoholic fatty liver disease (NAFLD) are high prevalence, inter-related conditions at increased risk for advanced liver diseases and related mortality. Adiponectin and leptin have divergent roles in the pathogenesis of fat accumulation and NAFLD. However, the relationships between body and liver fat accumulation, early modification of liver function and unbalanced adipokine levels are still scarcely explored. We studied by (13C)-methacetin breath test ((13C)-MBT) 67 adults stratified according to body mass index, and to presence/absence of ultrasonographic nonalcoholic fatty liver disease (uNAFLD). uNAFLD was detected in 20%, 73% and 96% of normal weight, overweight and obese subjects, respectively. The delta over baseline after 15 min (DOB15), a marker of hepatic extraction efficiency from portal blood flow, was lower in obese than in normal weight subjects, and in subjects with-, as compared to those without uNAFLD. The cumulative percent dose recovery after 30 min (cPDR30), a marker of liver microsomal function, was lower in uNAFLD patients. DOB15 was positively correlated with adiponectin levels in obese and in uNAFLD patients. uNAFLD patients also showed a positive correlation between cPDR30 values and adiponectin. Our data indicate the existence of early alterations of liver function in obese and in patients with uNAFLD. These dysfunctions are linked to altered leptin/adiponectin balance and can be identified noninvasively by (13C)-MBT.

Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.

Consumption of natural products such as herbs, spices, plant-derived compounds, and foods is on the rise globally. The use of these substances is widely recognized as an integral part of culture and tradition, with the philosophy being “no benefit is no harm”. The utility of medicinal plants and extracts is under scrutiny, and the scientific community needs to clarify many conceptual gaps. Medicinal plants are rich in bioactive phytochemicals that produce chemopreventive effects at different levels, including cellular, animal, and clinical. The ultimate translational value is often missing, and some studies suggest that botanicals may contain toxic compounds that cause acute or chronic toxicity. In this regard, the liver is the center, and herbal products can show protective effects or induce hepatotoxicity, thereby promoting liver cancer. In this review article, we examine a range of herbal products implicated in hepatocarcinogenesis and extend the discussion to herbal products that may be potentially involved in the prevention and treatment of liver carcinoma.

Background & Aims: H. pylori eradication is strongly affected by various factors, including the ongoing antibiotic resistance. We describe a “real life” scenario in patients managed for H. pylori-related conditions, living in a southern Italian region (Apulia), an area with clarithromycin resistance >15%.Methods: 2,224 subjects were studied in two tertiary referral centers in Apulia. Analyses included: reason for referral, H. pylori infection rates (13C-urea breath test – UBT or upper endoscopy), and eradication rates following distinct regimens previously prescribed or prospectively prescribed (such as the bismuth-based quadruple therapy Pylera®, recently marketed in Italy).Results. Over 80% of the patients were referred by family physicians (60% naïve subjects). The overall infection rate was 32.5% and it was similar in asymptomatic patients (31.1%) or with H. pylori-related symptoms/clinical conditions (34.3%). In the 987 H. pylori+ve patients receiving therapy, the overall eradication rate was 80.2% (ITT). Observed eradication rate varied greatly across different regimens: 57.1% (2nd line levofloxacin), 59.6% (unconventional), 70.7% (7-day triple), 73.2% (7-day undefined), 89% (10-day sequential) and 96.9% (ITT, 10 day Pylera®, 1st to 5th line regimens given to 227 patients).Conclusions. A heterogeneous “real life” scenario in Southern Europe shows that H. pylori+ve patients are put at risk of poor outcomes and points to the need of a susceptibility-based therapy according to guidelines and local microbial resistance. In the present setting (i.e. high clarithromycin resistance), despite the high observed eradication rate, sequential therapy should not be recommended (absent in guidelines, unneeded antibiotic). Bismuth-based quadruple treatment (1st, 2nd or subsequent lines) yields the highest eradication rates.Abbreviations: ALT: Altamura; BA: Bari; EGDS: esophagogastroduodenoscopy; GERD: gastro-esophageal reflux disease; H. pylori: Helicobacter pylori; ITT: intention-to-treat; PP: per-protocol; PPI: proton pump inhibitor; UBT: urea breath test.

BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, which still lacks effective therapy. We aimed to investigate the effects of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 with vitamin B6 (LBB) on symptoms, intestinal permeability, cultivable bacteria and metabolome in IBS subjects. MATERIALS AND METHODS Twenty-five IBS patients (Rome IV criteria) (M:F = 8:17; age 48 years ± 11 SD) were randomized to treatment (LBB) or placebo (one month each) in a crossover randomized double-blind controlled trial. Symptoms, intestinal habits, disease severity, intestinal permeability and intestinal microbiota were analysed at 0, 30, 45 and 60 days. RESULTS Percentage decrease from baseline of abdominal pain (-48.8% vs -3.5%), bloating (-36.35% vs +7.35%) and severity of disease (-30.1% vs -0.4%) was significantly (P

Background & Aims: 13 C-Urea Breath Test (UBT) is a non-invasive, highly accurate and recommended test to detect Helicobacter pylori (H. pylori) infection and to confirm post-therapy eradication. However, differences exist in terms of manufacturers, dose of labelled urea, addition of citric acid, solid vs. liquid formulation, and sampling times of breath samples. In this study, we compared the diagnostic accuracy of “short” (15 minutes) vs. “standard” (30 minutes) time for a single type of liquid UBT. Methods: We compared the performance of a single UBT type (BREATHQUALITY, AB Analitica, Padua, Italy, 10 mL of 75 mg 13 C-Urea and 1.4 g citric acid) during a “short” vs. “standard” breath sampling time. Enrolled were 151 subjects requiring UBT as naïve (N=92) or post-eradication (N=59) checks. Results: UBT at 15 and 30 minutes were highly comparable, showing optimal correlation in all subsets of patients (i.e. naïve vs. post eradication, negative vs. post eradication check). One discrepant result occurred at the borderline zone of the DOB 4‰, but proved to be true positive at a later confirmation by a second UBT and stool antigen test. Conclusions: By shortening the testing time of BREATHQUALITY to 15 minutes (-50%) comparable accuracy will be maintained and in addition, it will bring some benefits to patients’ waiting lists, compliance, and hospital staff.

Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.

Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most commonly diagnosed gastrointestinal diseases. The impact of IBS on the general population is large due to its high prevalence, suboptimal medical treatments and significant economic burden. The pathophysiology of IBS is complex and treatments are often symptom-specific. The most common therapeutic approaches for IBS include education and reassurance, lifestyles (especially nutrition-based interventions), peripherally acting medications (which typically target motility), centrally acting medications (which target visceral hypersensitivity and pain) and psychological interventions (which aim to reduce the effects of stress or symptom-specific anxiety). A beneficial dietary approach might include the following measures: a diet low in fermentable oligo-,di- and monosaccharides and polyols (FODMAPs), limitation or exclusion of gas-producing foods and/or lactose and gluten and fiber supplementation in selected cases. New therapeutic agents, namely nutraceutics, are also an interesting option in the management of IBS patients. This paper will focus on available dietary interventions for IBS and will review the evidence for nutrition-based therapies.

The gastrointestinal tract hosts the natural reservoir of microbiota since birth. The microbiota includes various bacteria that establish a progressively mutual relationship with the host. Of note, the composition of gut microbiota is rather individual-specific and, normally, depends on both the host genotype and environmental factors. The study of the bacterial profile in the gut demonstrates that dominant and minor phyla are present in the gastrointestinal tract with bacterial density gradually increasing in oro-aboral direction. The cross-talk between bacteria and host within the gut strongly contributes to the host metabolism, to structural and protective functions. Dysbiosis can develop following aging, diseases, inflammatory status, and antibiotic therapy. Growing evidences show a possible link between the microbiota and Familial Mediterranean Fever (FMF), through a shift of the relative abundance in microbial species. To which extent such perturbations of the microbiota are relevant in driving the phenotypic manifestations of FMF with respect to genetic background, remains to be further investigated.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and parallels comorbidities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. Recent studies describe the presence of NAFLD in non-obese individuals, with mechanisms partially independent from excessive caloric intake. Increasing evidences, in particular, point towards a close interaction between dietary and environmental factors (including food contaminants), gut, blood flow, and liver metabolism, with pathways involving intestinal permeability, the composition of gut microbiota, bacterial products, immunity, local, and systemic inflammation. These factors play a critical role in the maintenance of intestinal, liver, and metabolic homeostasis. An anomalous or imbalanced gut microbial composition may favor an increased intestinal permeability, predisposing to portal translocation of microorganisms, microbial products, and cell wall components. These components form microbial-associated molecular patterns (MAMPs) or pathogen-associated molecular patterns (PAMPs), with potentials to interact in the intestine lamina propria enriched in immune cells, and in the liver at the level of the immune cells, i.e., Kupffer cells and stellate cells. The resulting inflammatory environment ultimately leads to liver fibrosis with potentials to progression towards necrotic and fibrotic changes, cirrhosis. and hepatocellular carcinoma. By contrast, measures able to modulate the composition of gut microbiota and to preserve gut vascular barrier might prevent or reverse NAFLD.

Background and aim Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. Materials and methods Forty-six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. Results Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. Conclusion Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.

As a staple food, bread digestibility deserves a marked nutritional interest. Combining wide-spectrum characterization of breads, in vitro nutritional indices, and in vivo postprandial markers of gastrointestinal function, we aimed at comparing the digestibility of sourdough and baker&rsquo, s yeast breads. Microbiological and biochemical data showed the representativeness of the baker&acute, s yeast bread (BYB) and the two sourdough breads (SB and t-SB, mainly differing for the time of fermentation) manufactured at semi-industrial level. All in vitro nutritional indices had the highest scores for sourdough breads. Thirty-six healthy volunteers underwent an in vivo challenge in response to bread ingestion, while monitoring gallbladder, stomach, and oro-cecal motility. SB, made with moderate sourdough acidification, stimulated more appetite and induced lower satiety. t-SB, having the most intense acidic taste, induced the highest fullness perception in the shortest time. Gallbladder response did not differ among breads, while gastric emptying was faster with sourdough breads. Oro-cecal transit was prolonged for BYB and faster for sourdough breads, especially when made with traditional and long-time fermentation (t-SB), whose transit lasted ca. 20 min less than BYB. Differences in carbohydrate digestibility and absorption determined different post-prandial glycaemia responses. Sourdough breads had the lowest values. After ingesting sourdough breads, which had a concentration of total free amino acids markedly higher than that of BYB, the levels in blood plasma were maintained at constantly high levels for extended time.

Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor.

OBJECTIVE Fructose is absorbed by GLUT transporters in the small intestine. If this process is inadequate, abdominal symptoms because of fructose intolerance may arise. The effect of a tailored fructose-restricted diet on gastrointestinal complaints was assessed in patients with fructose intolerance. MATERIALS AND METHODS Following an abnormal fructose breath test (50 g), 107 patients (64 also with lactose intolerance) entered three study periods: weeks 0-32 (free diet), weeks 32-36 (progressive increasing amount of fructose up to quantity inducing symptoms, 'trigger dose'), and weeks 36-48 (tailored fructose-restricted diet according to the 'trigger dose'). A subgroup of 15 patients underwent additional fructose breath tests (35, 25 g) to compare three different doses. RESULTS At baseline, the most frequent symptoms were bloating and abdominal pain, and were more severe with combined fructose and lactose intolerance. During the free diet, patients reported eliminating (48%) or reducing (52%) fructose-containing foods, with a significant improvement in symptoms (abdominal pain from 79.7 ± 1.3 to 19.3 ± 1.8 mm; bloating from 83.1 ± 1.3 to 19.4 ± 1.8 mm; number of evacuations/day from 3.9 ± 0.16 to 1.1 ± 0.04; Bristol score from 5.1 ± 0.14 to 3.8 ± 0.1, P < 0.00001). During the tailored fructose-restricted diet, the consistent improvement in symptoms persisted and was similar to the improvement on free diet (abdominal pain 23.6 ± 1.9 mm; bloating 19.4 ± 1.8 mm; number of evacuations/day 1.7 ± 0.07; Bristol score 3.5 ± 0.06, P

The primary bile acids (BAs) are synthetized from cholesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat. BAs are also bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolismby activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.

Background Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterised by recurrent attacks of fever and serositis (peritonitis, pleuritic or synovitis) affecting mainly populations of Mediterranean origin. Aim To describe a relatively new cluster of FMF subjects from Apulia and Basilicata regions (southern Italy). Patients and methods Subjects were screened for FMF using the Tel-Hashomer criteria and genetic analysis. Demographic data were taken from patients’ files and direct interviews. Patients were investigated about attack duration, intensity and site, body temperature, skin manifestations and overall quality of life before and after treatment with colchicine. Inflammatory parameters were also measured between these periods. Results Forty-nine subjects had FMF (M : F = 26 : 23, age 38 years ± 2 SE) and followed-up up to 8 years. The age at disease onset was 22·1 years ± 1·2SE and the diagnostic delay was 15·5 years ± 1·9SE. The majority of patients (82%) suffered from abdominal pain, and 35% had undergone prior abdominal surgery or laparotomy. Severity score (ISSF) was mild in 43% of patients and intermediate in 57% of patients. Serum amyloid A (SAA) was increased in 20% of patients (16·9 ± 3·7, normal range < 6·4 mg/dL). In over 95% of patients, inflammation markers, duration and intensity of febrile painful attacks, quality of life and ISSF score improved dramatically following colchicine treatment. Conclusion The Apulia region represents a new endemic area for FMF. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognise the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long-term complications.

In gastroenterological practice, breath tests (BTs) are diagnostic tools used for indirect, non-invasive assessment of several pathophysiological metabolic processes, by monitoring the appearance in breath of a metabolite of a specific substrate. Labelled substrates originally employed radioactive carbon 14 ((14)C) and, more recently, the stable carbon 13 isotope ((13)C) has been introduced to label specific substrates. The ingested (13)C-substrate is metabolized, and exhaled (13)CO2 is measured by mass spectrometry or infrared spectroscopy. Some (13)C-BTs evaluate specific (microsomal, cytosolic, and mitochondrial) hepatic metabolic pathways and can be employed in liver diseases (i.e. simple liver steatosis, non-alcoholic steato-hepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug and alcohol effects). Another field of clinical application for (13)C-BTs is the assessment of gastric emptying kinetics in response to liquids ((13)C-acetate) or solids ((13)C-octanoic acid in egg yolk or in a pre-packed muffin or the (13)C-Spirulina platensis given with a meal or a biscuit). Studies have shown that (13)C-BTs, used for gastric emptying studies, yield results that are comparable to scintigraphy and can be useful in detecting either delayed- (gastroparesis) or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects. Thus, (13)C-BTs represent an indirect, cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease, and several other potential applications are being studied.

Obesity is a risk factor for the formation of cholesterol gallstones and exposes patients to increased risk of gallstone-related complications and cholecystectomy. Rapid weight loss achieved by very low calorie diets or bariatric surgery is also a risk factor for cholelithiasis in obese patients, and therapy should take into account the higher prevalence of gallstones, the possibility of more frequent complications and the need for prophylactic treatment with oral ursodeoxycholic acid during weight loss. Obesity is also frequent in children and adolescents, and the burden of cholesterol cholelithiasis is increasing in this population. The chance to develop acute pancreatitis and the severity of the disease are higher in obese subjects because of specific pathogenic factors, including supersaturated bile and crystal formation, rapid weight loss, and visceral obesity. All health policies aimed at reducing the incidence of obesity worldwide will decrease the incidence of gallstones and gallstone-related complications. The pathophysiological scenarios and the therapeutic implications for obesity, gallstone disease, and pancreatitis are discussed.

Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influence the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota.

Menopause is a consequence of the normal aging process in women. This fact implies that the physiological and biochemical alterations resulting from menopause often blur with those from the aging process. It is thought that menopause in women presents a higher risk for cardiovascular disease although the precise mechanism is still under discussion. The postmenopause lipid profile is clearly altered, which can present a risk factor for cardiovascular disease. Due to the role of mitochondria in fatty acid oxidation, alterations of the lipid profile in the menopausal women will also influence mitochondrial fatty acid oxidation fluxes in several organs. In this paper, we propose that alterations of mitochondrial bioenergetics in the heart, consequence from normal aging and/or from the menopausal process, result in decreased fatty acid oxidation and accumulation of fatty acid intermediates in the cardiomyocyte cytosol, resulting in lipotoxicity and increasing the cardiovascular risk in the menopausal women.