Is the Mediterranean Low Fodmap Diet Effective in Managing Irritable Bowel Syndrome Symptoms and Gut Microbiota? An Innovative Research Protocol.

INTRODUCTION: Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases. AIM: To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life. MATERIALS AND METHODS: Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED's anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708.

Evolution, adaptation, and new applications of the FODMAP diet.

The FODMAP diet has been a treatment of irritable bowel syndrome (IBS) for many years. Rigorous scientific evaluation and clinical application of the FODMAP diet have generated deep understanding regarding clinical efficacy, mechanisms of action, and potential adverse effects of this dietary approach. In turn, this knowledge has allowed fine-tuning of the diet to optimize treatment benefits and minimize risks, in the form of the traditional three-phase diet; the FODMAP-gentle approach, which is a less restrictive iteration; and a proposed FODMAP-modified, Mediterranean-style diet which endeavours to optimise both gastrointestinal symptoms and other health parameters. Furthermore, recognition that IBS-like symptoms feature in other conditions has seen the FODMAP diet tested in non-IBS populations, including in older adults with diarrhea and women with endometriosis. These areas represent new frontiers for the FODMAP diet and a space to watch as future research evaluates the validity of these novel clinical applications.

Translation, validation, and first application of the Greek version of an irritable bowel syndrome severity scoring system.

Background: The Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) is a self-administered questionnaire that categorizes patients according to symptom severity. We aimed to translate and adapt the English IBS-SSS, validate the Greek version, and detect factors predictive of IBS severity. Methods: The original English version was obtained from the Rome Foundation, and the final Greek version arose through a process of translation, comprehensibility evaluation and back-translation. The 141 participants enlisted in the study were enrolled from 2 tertiary hospitals and were divided into 2 groups (98 patients and 43 healthy volunteers). We evaluated the questionnaire properties based on COSMIN criteria. Results: The recruited patients reported either diarrhea-predominant (34.7%), constipation-predominant (28.6%), or mixed subtype (36.7%) IBS. No significant variations were found regarding the frequency and intensity of abdominal pain and flatulence among the 3 IBS subtypes. Severity scores among healthy volunteers were significantly lower compared to IBS patients, irrespective of their disease subtype (P<0.001). The Cronbach coefficient (α) was calculated at 0.953, suggesting high inter-item internal consistency. The intraclass correlation coefficient was calculated and found to be high, suggesting good responsiveness of the questionnaire. Two-way MANOVA evaluation showed that demographic variables (age, family status, body mass index [BMI], smoking, and alcohol consumption) in the Greek population affect the IBS-SSS score and syndrome severity. Conclusions: The Greek version of IBS-SSS is a reliable, valid and responsive tool for assessing Greek IBS patients' symptom severity. Older age, smoking, alcohol use and higher BMI are indicative of greater symptom severity.

The Low-FODMAP Diet, IBS, and BCFAs: Exploring the Positive, Negative, and Less Desirable Aspects-A Literature Review.

The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized by low-grade inflammation and intestinal dysbiosis. The low-FODMAP diet (LFD) has increasingly been applied as first-line therapy for managing IBS symptoms, although it decreases the production of short-chain fatty acids (SCFA), well known for their anti-inflammatory action. In parallel, high protein consumption increases BCFAs. Protein fermentation alters the colonic microbiome through nitrogenous metabolites production, known for their detrimental effects on the intestinal barrier promoting inflammation. Purpose: This review aims to explore the role of BCFAs on gut inflammation in patients with IBS and the impact of LFD in BCFAs production. Methods: A literature search was carried out using a combination of terms in scientific databases. Results: The included studies have contradictory findings about how BCFAs affect the intestinal health of IBS patients. Conclusions: Although evidence suggests that BCFAs may play a protective role in gut inflammation, other metabolites of protein fermentation are associated with gut inflammation. Further research is needed in order to clarify how diet protein composition and, consequently, the BCFAs are implicated in IBS pathogenesis or in symptoms management with LFD+.

The Level of Adherence to the ESPEN Guidelines for Energy and Protein Intake Prospectively Influences Weight Loss and Nutritional Status in Patients with Cancer.

Nutrition therapy aims to prevent weight loss and its health consequences in patients with cancer. The aim of this study was to assess Greek patients' adherence to the ESPEN guidelines for oncology patients and its prospective effect on their body weight (BW) and nutritional status. In total, 152 patients with cancer were recruited from the Attikon University Hospital, Greece, and provided data in 2019 (baseline) and 2020 (follow-up) (drop-out rate = 28.3%). Nutritional status was assessed with the PG-SGA questionnaire. Patients were categorized based on whether they adhered at least to the minimum ESPEN-recommended intakes of energy (≥25 kcal/kg/day) or protein (≥1.0 g/kg/day) or not. On average, patients did not adhere to ESPEN guidelines for energy and protein intake. Most patients meeting the minimum recommendations had an improvement of their nutritional status at follow-up and increased their BW compared to those not meeting them. All patients with head, neck, and spinal cancer who met the minimum recommendations for energy intake improved their nutritional status at follow-up. This study showed that consuming at least the minimum amounts of protein and energy recommended by ESPEN may prevent from weight loss and improve nutritional status; however, the exact amounts need to be personalized.

Depression and Anxiety Mediate the Associations between Nutritional Status, Functional Capacity, and Quality of Life in Patients with Cancer.

Cancer patients are at risk of malnutrition, which influences their functional status, mental health (MH), and quality of life (QoL). This study aimed to examine the associations between nutritional status, functional capacity, and aspects of QoL in cancer patients, as well as the potential mediating role of depression and anxiety in these associations. Patients with various types of cancer (n = 152) were recruited from the Attikon University Hospital, Greece. Validated questionnaires were used to assess nutritional status (PG-SGA), QoL (SF-36 and EQ-5D-3L), functional capacity (ECOG), depression, and anxiety (HADS and BEDS). Handgrip strength (HGS) was also measured. Poor nutritional status was inversely associated with functional capacity, QoL, depression, and anxiety, after adjusting for confounding factors (all P ≤ 0.05). Mediation analysis indicated a significant indirect effect of nutritional status on various parameters of functional capacity and QoL through depression and anxiety, after adjusting for age and sex. Mediated proportion ranged from 26.3-34% to 23.1-82.8% for functional capacity and QoL, respectively. A significant proportion of the effect of nutritional status on QoL and functional capacity can be partly attributed to psychological effects, highlighting the significance of integrating all aforementioned aspects in the nutritional intervention for cancer patients.

The Impact of Obesity on Perioperative Outcomes for Children Undergoing Appendectomy for Acute Appendicitis: A Systematic Review.

Today, the prevalence of obesity in the pediatric population has increased dramatically. Acute appendicitis (AA) is the most common surgical condition among pediatric patients. We aimed to investigate the impact of obesity on postoperative outcomes in terms of operative time (OT), length of stay (LOS), surgical site infection (SSI), overall complications, adverse events, and mortality in children undergoing appendectomy for acute appendicitis. An extensive search of the literature in PubMed and Google Scholar was conducted to evaluate the outcomes of normal weight (NW), overweight (OW), and obese (OB) children who underwent appendectomy. Although no statistically significant differences were noted in perioperative outcomes and overall postoperative complications between OW/OB and NW children in the majority of the included studies, prolonged OT and LOS and SSI were found in some studies. Moreover, no differences in terms of readmissions and ED visits were recorded. We conclude that the impact of obesity on postoperative outcomes for children undergoing appendectomy for AA is unclear, and, therefore, no safe conclusions can be drawn with the currently available data. Due to the lack of high-quality studies, further research is required to optimize the surgical approach and prevent unwarranted complications.

Factors Associated with Interruptions of Enteral Nutrition and the Impact on Macro- and Micronutrient Deficits in ICU Patients.

BACKGROUND AND AIM: Feeding interruptions in critical care patients are often unjustified. We aimed to determine the causes, duration, and frequency of enteral nutrition interruptions (ENIs) and to assess macronutrients and antioxidant deficits according to European Society of Parenteral Enteral Nutrition (ESPEN) guidelines. METHODS: We prospectively enrolled Intensive Care Unit (ICU) patients admitted for more than 48 h with an inability to orally eat from April to December 2019. The type of enteral nutrition, the number of calories administered, the time of feeding initiation, the reasons for delaying feeding, and the causes for ENI were recorded. RESULTS: 81 patients were enrolled, with a median duration of ENIs of 5.2 (3.4-7.4) hours/day. Gastric residual volume (GRV) monitoring-a highly controversial practice-was the most common cause of ENI (median duration 3 (2.3-3) hours/day). The mean energy intake was 1037 ± 281 kcal/day, while 60.5% of patients covered less than 65% of the total energy needs (1751 ± 295 kcal/day, according to mean Body Mass Index (BMI)). The median daily protein intake did not exceed 0.43 ± 0.3 gr/kg/day of the actual body weight (BW), whereas ESPEN recommends 1.3 gr/kg/day for adjusted BW (p < 0.001). The average administration of micronutrients and antioxidants (arginine, selenium, zinc, vitamins) was significantly less than the dietary reference intake (p < 0.01). CONCLUSION: ENIs lead to substantial caloric, protein, and antioxidant deficits.

Immunomodulatory Effects of Probiotics on COVID-19 Infection by Targeting the Gut-Lung Axis Microbial Cross-Talk.

The ecosystem of the human gastrointestinal tract, named gut microbiota, represents the most thoroughly mapped ecosystem. Perturbations on bacterial populations cause dysbiosis, a condition correlated to a wide range of autoimmune, neurological, metabolic, cardiovascular, and respiratory diseases. The lungs have their flora, which are directly related to the gut flora via bidirectional communication allowing the transport of microbial metabolites and toxins produced by intestinal bacteria through the circulation and lymphatic system. This mutual microbial cross-talk communication called the gut-lung axis modulates the immune and inflammatory response to infections. COVID-19 causes dysbiosis, altered intestinal permeability, and bacterial translocation. Dysbiosis, through the gut-lung axis, promotes hyper-inflammation, exacerbates lung damage, and worsens clinical outcomes. Preclinical and clinical studies have shown that probiotics can regulate cytokine secretion, thus affecting both nonspecific and specific immunity. Probiotics act by blocking the virus from invading and proliferating in host cells, by stimulating the immune response, and by suppressing the activation of NLRP3 inflammasome. Herein, we reviewed the evidence from preclinical and clinical studies evaluating the effect of probiotics administration on the immune response to COVID-19 infection by targeting the gut-lung axis microbial cross-talk.

The Effects of Stevia Consumption on Gut Bacteria: Friend or Foe?

Stevia, a zero-calorie sugar substitute, is recognized as safe by the Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). In vitro and in vivo studies showed that stevia has antiglycemic action and antioxidant effects in adipose tissue and the vascular wall, reduces blood pressure levels and hepatic steatosis, stabilizes the atherosclerotic plaque, and ameliorates liver and kidney damage. The metabolism of steviol glycosides is dependent upon gut microbiota, which breaks down glycosides into steviol that can be absorbed by the host. In this review, we elucidated the effects of stevia's consumption on the host's gut microbiota. Due to the lack of randomized clinical trials in humans, we included in vitro using certain microbial strains and in vivo in laboratory animal studies. Results indicated that stevia consumption has a potential benefit on the microbiome's alpha diversity. Alterations in the colonic microenvironment may depend on the amount and frequency of stevia intake, as well as on the simultaneous consumption of other dietary components. The anti-inflammatory properties of stevioside were confirmed in vitro by decreasing TNF-α, IL-1ß, IL-6 synthesis and inhibiting of NF-κB transcription factor, and in vivo by inhibiting NF-κB and MAPK in laboratory animals.

A Combination of Mediterranean and Low-FODMAP Diets for Managing IBS Symptoms? Ask Your Gut!

Among other factors, food intolerance is cardinal in triggering irritable bowel syndrome (IBS) symptoms in a significant percentage of patients. As a result, specific dietary patterns are the first-line therapeutic approach. The low-FODMAP diet (LFD) is gaining ground as the most well-documented diet intervention that significantly reduces IBS symptoms. Though the LFD improves symptoms, the diet's impact on intestinal low-grade inflammation, one of the cardinal mechanisms contributing to symptom development, remains doubtful. On the other hand, the Mediterranean diet (MedDiet) is recommended for chronic low-grade inflammation-related diseases because of its anti-inflammatory properties, derived predominantly from olive oil and phenolic compounds. Thus far, the role of a modified LFD, enriched with the MedDiet's anti-inflammatory components, has not been evaluated in IBS patients. This review aims to examine the hypothesis of a potential combination of the immunomodulatory effects of the MedDiet with the LFD to improve IBS symptoms.

Intensive nutrition support may benefit patients with a rare mitochondrial disorder.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare, inherited, multisystemic autosomal recessive disorder caused by mutations in the nuclear TYMP gene. This syndrome is characterized by ptosis, external ophthalmoplegia, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and leukoencephalopathy. Our case illustrates a patient diagnosed with MNGIE and cachexia who has benefited from the initiation and maintenance of parenteral nutrition. We highlight the benefits of receiving long-term supplementary home parenteral nutrition under close monitoring for patients with this neurogastrointestinal disease in order to gain weight and maintain good health.

Probiotics Regulating Inflammation via NLRP3 Inflammasome Modulation: A Potential Therapeutic Approach for COVID-19.

Inflammasomes are cytoplasmic multiprotein complexes formed by the host's immune system as a response to microbial infection and cellular damage. Many studies have revealed various regulators of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation, while it has been recently shown that NLRP3 is implicated in COVID-19 pathogenesis. At the same time, probiotics counteract the inflammatory process and modulate cytokine release, thus influencing both innate and adaptive immune systems. Herein, we review the immunomodulatory potential of probiotics on the assembly of NLRP3 inflammasome, as well as the pathophysiological mechanisms supporting the use of probiotic bacteria for SARS-CoV-2 infection management, presenting evidence from preclinical studies of the last decade: in vivo, ex vivo, and mixed trials. Data show that probiotics intake is related to NLRP3 inflammasome attenuation and lower levels of inflammation markers, highlighting the beneficial effects of probiotics on inflammatory conditions. Currently, none of the ongoing clinical trials evaluating the effectiveness of probiotics intake in humans with COVID-19 has been completed. However, evidence from preclinical studies indicates that probiotics may block virus invasion and replication through their metabolites, bacteriocins, and their ability to block Angiotensin-Converting Enzyme 2 (ACE2), and by stimulating the immune response through NLRP3 inflammasome regulation. In this review, the beneficial effects of probiotics in the inflammatory process through NLRP3 inflammasome attenuation are presented. Furthermore, probiotics may target SARS-CoV-2 both by blocking virus invasion and replication and by stimulating the immune response through NLRP3 inflammasome regulation. Heterogeneity of the results-due to, among others, different bacterial strains and their metabolites, forms, dosage, and experimental designs-indicates the need for more extensive research.

True Restriction in Diffusion-Weighted Imaging in a Mistreated Patient With Phenylketonuria.

INTRODUCTION: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism and causes neurological manifestations because of excessive accumulation of phenylalanine (PHE). It can also affect adult patients who discontinue their treatment, even if they had been under adequate metabolic control during childhood. For that reason, it is recommended that PKU treatment should be continued throughout life and target PHE levels for adult patients should range between 120 and 600 µmol/L. CASE REPORT: The authors present an adult patient with PKU who discontinued treatment and developed cognitive dysfunction because of high blood levels of PHE. Brain magnetic resonance imaging (MRI) of the patient was characteristic for PKU, presenting periventricular and callosal white matter hyperintensities in T2 and fluid-attenuated inversion recovery sequences, which were additionally associated with true restriction in diffusion-weighted imaging sequence, a far less recognized PKU neuroimaging feature. DISCUSSION: Cognitive dysfunction and psychiatric disorders can be present in adult patients with PKU who discontinue treatment and have poor PHE metabolic control. The presence of white matter hyperintensities in T2 and fluid-attenuated inversion recovery MRI-sequences is a well-described neuroimaging feature of PKU, but diffusion-weighted imaging sequence may also be reliable in detecting brain lesions in patients with PKU. PKU lesions should be considered in the differential diagnosis of true diffusion restriction in brain MRI of patients with PKU history or those who might have escaped newborn screening diagnosis but present neurocognitive dysfunction. Appropriate treatment for the management of PKU should be initiated for the reversal of the clinical and neuroimaging findings.