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Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition

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A Special Issue of Life (ISSN 2075-1729) belonging to the section "Medical Research".

Deadline for manuscript submissions: closed (2 September 2026) | Viewed by 7760

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Editors

Prof. Dr. Ludovico Abenavoli

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Guest Editor

Department of Health Sciences, University "Magna Græcia", Campus Germaneto, I-88100 Catanzaro, Italy
Interests: metabolic liver disease; alcohol-related liver disease; gut microbiota; Mediterranean diet; nutrition; probiotic
Special Issues, Collections and Topics in MDPI journals

Dr. Giuseppe Guido Maria Scarlata

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Guest Editor

Department of Health Sciences, University “Magna Graecia”, 88100 Catanzaro, Italy
Interests: gut–liver axis; gut microbiota; fatty liver disease; viral hepatitis; COVID-19; antimicrobial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to warmly invite you to contribute to the second edition of the Special Issue “Gastrointestinal Health: Clinical Research and Therapeutic Innovations”.

This Special Issue will comprise a collection of original studies and reviews that explore the dynamic landscape of gastroenterology. This project will highlight pivotal advancements in diagnostic methodologies, therapeutic strategies, and clinical practices designed to enhance gastrointestinal health. Contributions will report on novel treatments for common gastrointestinal disorders, including irritable bowel syndrome, inflammatory bowel disease, and gastroesophageal reflux disease. At the same time, conditions affecting the liver, such as fatty liver disease, liver cirrhosis, and hepatocellular carcinoma, will also be addressed. Key focus areas include the gut microbiota's role in health and disease and investigations into the therapeutic potential of probiotics, prebiotics, and dietary interventions. This Special Issue will also address challenges and opportunities in translating basic research findings into clinical practice, fostering a holistic understanding of gastrointestinal health. Multidisciplinary perspectives will be emphasized, integrating insights from gastroenterologists, hepatologist, nutritionists, microbiologists, and clinical researchers. This collaborative approach will allow us to bridge the gap between laboratory research and bedside application, promoting evidence-based innovations that can be readily adopted in clinical settings. Overall, this Special Issue will serve as an invaluable resource for clinicians, researchers, and healthcare professionals dedicated to advancing the field of gastroenterology. By highlighting the latest clinical research and therapeutic innovations, it will enhance patient care, improve health outcomes, and pave the way for future discoveries in gastrointestinal health.

Prof. Dr. Ludovico Abenavoli
Dr. Giuseppe Guido Maria Scarlata
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

gut microbiota
inflammatory bowel diseases
irritable bowel syndrome
gastroesophageal reflux disease
fatty liver disease
liver cirrhosis
probiotics
mediterranean diet
epidemiology
diagnosis
treatment
artificial intelligence

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Published Papers (8 papers)

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Research

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15 pages, 281 KB

Open AccessArticle

Comparative Effectiveness of Mebeverine and Otilonium Bromide on Health-Related Quality of Life in Patients with Irritable Bowel Syndrome: A Prospective Cohort Study

by Anh Thi Phuong Luu and Thong Duy Vo

Life 2026, 16(9), 1390; https://doi.org/10.3390/life16091390 - 24 Aug 2026

Viewed by 189

Abstract

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder that significantly impairs patients’ quality of life. Antispasmodics such as mebeverine and otilonium bromide (OB) are commonly used as first-line therapies; however, comparative evidence regarding their effectiveness and safety profile remains limited. This study aimed to compare short-term changes in health-related quality of life and the occurrence of adverse events among IBS patients receiving mebeverine or otilonium bromide. A prospective cohort study was conducted from December 2024 to July 2025 among 110 IBS patients meeting the Rome IV criteria who received either mebeverine 200 mg or OB 40 mg twice daily for 4 weeks. The IBS-specific quality-of-life questionnaire (IBS-QOL) was interviewer-administered at baseline and after treatment (week 4). Adverse drug events were documented and classified according to the Common Terminology Criteria for Adverse Events (CTCAE). After 4 weeks, significant within-group improvements in the overall IBS-QOL score and most domain scores were observed in both treatment groups. In the unadjusted between-group analysis, the mean improvement in the overall IBS-QOL score was greater in the mebeverine group than in the otilonium bromide group (20.31 ± 13.17 vs. 14.62 ± 14.61; p = 0.034). However, treatment group was not independently associated with change in the overall IBS-QOL score after multivariable adjustment (OB vs. mebeverine: B = −4.63, 95% CI −10.28 to 1.02; p = 0.107). Nominal differences in activity interference and health worry did not remain statistically significant after Holm correction for multiple domain-level comparisons. Adverse events occurred in 9 of 110 patients (8.2%), with no significant difference between the mebeverine and otilonium bromide groups (11.7% vs. 4.0%; Fisher’s exact p = 0.178). All reported events were mild. In this prospective observational cohort, both mebeverine and otilonium bromide use was associated with short-term improvement in health-related quality of life and low rates of mild adverse events. Although the unadjusted change in the overall IBS-QOL score favored mebeverine, the adjusted analysis did not establish an independent difference between the two treatments. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

18 pages, 10457 KB

Open AccessArticle

Preliminary In Silico Evaluation of Extra Virgin Olive Oil-Derived Bioactive Compounds as Multi-Target-Directed Ligands in Metabolic Dysfunction-Associated Steatotic Liver Disease

by Ludovico Abenavoli, Maja Milanović, Giuseppe Guido Maria Scarlata, Nataša Milošević, Maria Luisa Gambardella and Nataša Milić

Life 2026, 16(7), 1146; https://doi.org/10.3390/life16071146 - 10 Jul 2026

Viewed by 1028

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is driven by complex metabolic and inflammatory disturbances. Extra virgin olive oil (EVOO), a hallmark of the Mediterranean diet, contains numerous bioactive compounds that may exert beneficial effects on liver and cardiometabolic health. This preliminary study investigated the interactions of selected EVOO-derived compounds, with molecular targets implicated in MASLD using an integrated in silico approach. Methods: Phenolic compounds, secoiridoids, fatty acids, sterols, squalene, and vitamin E were evaluated. Physicochemical properties, drug-likeness, and pharmacokinetic profiles were predicted using ADMETlab 3.0. Molecular docking analyses were performed against liver X receptors (LXRα and LXRβ), peroxisome proliferator-activated receptors (PPARα and PPARγ), hydroxymethylglutaryl-CoA reductase, cyclooxygenase-1, and cyclooxygenase-2. Binding modes were further examined by three-dimensional interaction analyses. Results: The investigated compounds displayed heterogeneous physicochemical and pharmacokinetic profiles. Oleuropein, oleacein, and oleocanthal demonstrated the most consistent binding patterns across targets involved in lipid metabolism, inflammation, and cardiometabolic regulation. In contrast, highly lipophilic compounds, including squalene, β-sitosterol, and vitamin E, frequently achieved high docking scores but formed fewer biologically relevant interactions. Conclusions: EVOO phenolics, particularly oleuropein, oleacein, and oleocanthal, emerged as promising multi-target modulators of MASLD-related pathways, supporting the potential role of EVOO in MASLD prevention and management. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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25 pages, 3169 KB

Open AccessArticle

Muscle Function Impairment in Crohn’s Disease Patients: Risk Factors and Clinical Implications—Single-Tertiary-Center Experience

by Jelena Spiric Milovancevic, Aleksandar Toplicanin, Sasa Vuksanovic, Srdjan Djuranovic, Aleksandra Pavlovic Markovic, Sanja Mazic, Marina Djelic Blagojevic and Aleksandra Sokic-Milutinovic

Life 2026, 16(5), 790; https://doi.org/10.3390/life16050790 - 8 May 2026

Viewed by 459

Abstract

Sarcopenia in inflammatory bowel disease can significantly influence disease course. Since current assessment focuses mainly on muscle quantity, we aimed to evaluate muscle function in Crohn’s disease (CD) patients and identify those at increased risk of muscle function impairment. This cross-sectional study included 84 patients with CD (76.2% male, mean age 35 ± 11 years) receiving infliximab. Body composition was assessed by bioelectrical impedance analysis, muscle strength by handgrip strength (HGS), and physical performance by gait speed. Half of the cohort demonstrated reduced muscle strength relative to age- and sex-adjusted norms, while none met criteria for confirmed sarcopenia. One third of the patients had low physical performance and only one patient screened positive for sarcopenia. In multivariable linear regression, sex was the strongest independent predictor of HGS (p < 0.001), followed by ileocolonic disease localization, which was independently associated with lower HGS compared to ileal (p = 0.045) and colonic (p = 0.046). Hemoglobin remained an independent predictor of HGS after multivariable adjustment (p = 0.021). Low muscle strength is common in patients with CD treated with infliximab, even in the absence of low muscle mass. Ileocolonic disease localization and lower hemoglobin levels are predictors of low muscle strength, highlighting the importance of early and comprehensive muscle function assessment in this population. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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13 pages, 448 KB

Open AccessArticle

Impact of Disease Severity and Age on Outcomes After Laparoscopic Versus Open Appendectomy: A Single-Center Retrospective Cohort Study

by Nicolae-Dragoș Mărgăritescu, Stelian-Stefaniță Mogoantă, Tiberiu Stefăniță Țenea Cojan, Laurențiu Augustus Barbu and Liviu Vasile

Life 2026, 16(5), 706; https://doi.org/10.3390/life16050706 - 22 Apr 2026

Viewed by 614

Abstract

Background: Acute appendicitis is one of the most common surgical emergencies worldwide. This study aimed to evaluate the impact of disease severity and age on outcomes after laparoscopic versus open appendectomy and to identify predictors of prolonged hospitalization. Methods: A single-center retrospective cohort study was conducted at a tertiary emergency hospital, including 311 adult patients who underwent appendectomy between January 2020 and December 2024. The primary outcome was length of hospital stay (LOS), with prolonged hospitalization defined as LOS > 7 days. Results: The study included 311 patients (mean age 43.3 ± 18.0 years; 58.5% male), of whom 38.6% had complicated appendicitis. Complicated appendicitis was associated with older age and longer hospitalization. The laparoscopic approach was associated with a significantly shorter LOS compared with the open approach (4.43 ± 2.62 vs. 5.68 ± 3.11 days, p < 0.001). Increasing age independently predicted complicated appendicitis and prolonged hospitalization, while laparoscopy remained independently associated with reduced LOS after adjustment for measured confounders. No significant interaction was observed between surgical approach and disease severity. Conclusions: Disease severity and age are the main determinants of postoperative outcomes in acute appendicitis. Laparoscopic appendectomy was independently associated with shorter hospital stay after adjustment, although this association may be attenuated in more severe disease. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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14 pages, 304 KB

Open AccessArticle

Limited Predictive Value of NLR, PLR and SII in Thrombosed Hemorrhoids: A Real-World Analysis

by Liviu Vasile, Stelian-Stefaniță Mogoantă, Tiberiu-Ștefăniță Țenea-Cojan, Nicolae-Dragoș Mărgăritescu and Laurențiu Augustus Barbu

Life 2026, 16(4), 568; https://doi.org/10.3390/life16040568 - 31 Mar 2026

Viewed by 760

Abstract

Background: Systemic inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune inflammation index (SII) have been increasingly investigated as inexpensive biomarkers in various inflammatory and thrombotic conditions. However, their clinical utility in thrombosed hemorrhoids remains poorly defined. This study aimed to evaluate the diagnostic and predictive performance of NLR, PLR and SII in a real-world cohort of patients with hemorrhoidal disease. Methods: We conducted a retrospective observational study including 120 consecutive adult patients admitted with hemorrhoidal disease between January 2020 and December 2024. Systemic inflammatory indices were calculated from admission blood tests. Comparative analyses, receiver operating characteristic (ROC) curves, tertile trend assessment, and univariate and multivariable logistic regression models were used to evaluate the association between inflammatory indices and thrombosed hemorrhoids. Results: Thrombosed hemorrhoids were identified in 55.8% of patients. Median values of NLR, PLR and SII did not differ significantly between thrombosed and non-thrombosed cases (all p > 0.05). ROC analysis demonstrated poor discriminatory performance (AUC: 0.52 for NLR, 0.55 for PLR, and 0.51 for SII). In multivariable analysis adjusted for age, sex and bleeding status, none of the inflammatory indices were independently associated with thrombosed hemorrhoids (all p > 0.05). No significant trends were observed across NLR tertiles. Conclusions: In this real-world cohort, systemic inflammatory indices showed limited diagnostic and predictive value for thrombosed hemorrhoids. These findings suggest that routine inflammatory ratios provide minimal incremental benefit beyond standard clinical assessment in this predominantly localized benign anorectal condition. Further prospective multicenter studies exploring dynamic and tissue-level biomarkers are warranted. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

Review

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21 pages, 2570 KB

Open AccessReview

Interpreting Abdominal Surgical-Site Infection Trends Across the COVID-19 Shock: A Critical Narrative Review and the SSI Signal-Validity Framework

by Emil-Tiberius Trasca, Dumitru Radulescu, Eleonora Daniela Ciupeanu-Calugaru, Razvan Mercut, Vlad Dumitru Baleanu, Elena-Irina Caluianu, Alexandru-Marian Vieru and Patricia-Mihaela Radulescu

Life 2026, 16(8), 1320; https://doi.org/10.3390/life16081320 - 12 Aug 2026

Viewed by 308

Abstract

Background/Objectives: Comparisons of abdominal Surgical-Site Infection (SSI) rates during COVID-19 often treat recorded incidence as a direct measure of biological risk, although the pandemic altered operative volume and case mix, prevention practices, and post-discharge detection. This review examines when reported SSI changes are interpretable. Methods: We conducted a critical narrative review, informed by SANRA and critical interpretive synthesis, of MEDLINE/PubMed, Embase, Scopus, and Europe PMC (January 2018–25 June 2026). Comparative SSI studies formed the core evidence set, supported by contextual studies on emergency presentation, biological risk, prevention, and surveillance. Results: Studies reported lower, unchanged, non-monotonic, and higher SSI rates. These differences became more coherent when the recorded rate was separated into operative composition, true infection probability, and detection probability. No core study measured all domains required to isolate a biological pandemic effect. Evidence from acute pancreatitis and abdominal trauma showed that disease severity, care access, inflammatory status, and prognostic relationships varied with health-system context. Conclusions: We propose the Surgical-Site Infection Signal-Validity Framework (SSI-SVF). It classifies findings as probable true improvement, apparent improvement, masked deterioration, mixed deterioration, or indeterminate and requires joint assessment of operative composition, true infection risk, and detection probability before interpreting a calendar-period change as altered surgical safety. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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23 pages, 2019 KB

Open AccessReview

Gut Microbiota Biomarkers in Patients with Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors

by Maria Cerreto, Marta Maestri, Maria Pallozzi, Lucia Cerrito, Leonardo Stella, Gianluca Ianiro, Antonio Gasbarrini and Francesca Romana Ponziani

Life 2026, 16(4), 641; https://doi.org/10.3390/life16040641 - 10 Apr 2026

Viewed by 1072

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant role of the gut–liver axis in modulating immunotherapy outcomes, and several studies have identified distinct microbial features associated with either responders or non-responders. Responders to immunotherapy frequently present with higher microbial diversity and enrichment of beneficial taxa, whereas the expansion of pro-inflammatory and pathogenic bacteria has been associated with primary resistance and increased treatment-related toxicity in non-responders. However, the available findings remain heterogeneous across cohorts, likely owing to differences in geography, diet, liver disease etiology, treatment regimens, and microbiome analytical methods. Machine-learning models integrating metagenomic and metabolomic data have shown encouraging results in defining microbial signatures associated with treatment outcomes, although variability among cohorts currently limits their clinical applicability and generalizability. Beyond microbial taxonomic composition, microbiota-derived metabolites—such as short-chain fatty acids, bile acids, inosine, and tryptophan catabolites—appear to play a crucial role in shaping the tumor microenvironment and host immune responses, thus representing additional candidate biomarkers, also due to the relative ease of their measurement. Finally, microbiota-targeted interventions are emerging as potential strategies to enhance immunotherapy efficacy. Overall, the gut microbiome and its metabolic activity represent promising tools, albeit still under investigation, for patient stratification and personalized management in HCC treated with ICIs. Therefore, this review aims to summarize and critically discuss the current evidence on gut microbiota-derived biomarkers of response and resistance to ICIs in HCC, with particular focus on microbial composition, microbiota-related metabolites, and emerging microbiome-based therapeutic strategies. This narrative review provides an updated overview of the role of gut microbiota as both a biomarker and a therapeutic target in patients with hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitor (ICI) therapy. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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33 pages, 1446 KB

Open AccessReview

Bioengineering Interventions to Enhance the Capacity of the Gut Microbiota in Controlling Food Allergies

by Manish Kumar, Shivani Nalla, Jatindra N. Tripathy and Akhilesh Kumar Shakya

Life 2026, 16(3), 433; https://doi.org/10.3390/life16030433 - 7 Mar 2026

Viewed by 1894

Abstract

Food allergies arise when environmental factors, lifestyle choices, and genetic predispositions affect the integrity of the gut epithelial barrier. Under healthy conditions, gut microbiota supports intestinal tight junction integrity and promotes immune tolerance to dietary allergens. Disruption of this microbiota increases susceptibility to epithelial barrier leakage, thereby enabling food allergens to penetrate the bloodstream from the gut and leading to allergic sensitization. Restoring gut homeostasis through allergen-specific immunotherapy (AIT), executed via oral termed as oral immunotherapy (OIT), skin as subcutaneous immunotherapy (SCIT), or under the tongue in the form of sublingual immunotherapy (SLIT), remains a promising yet complex and multifaceted approach. In parallel, probiotics offer a simpler alternative to reinforce epithelial barrier function, restore cellular homeostasis, mitigate allergy symptoms, and represent the probiotics-based OIT. Recently, several bioengineering strategies have been developed toward enriching gut microbiota, such as using additives such as carbohydrates, polyphenols, and probiotics. While generic probiotics have shown efficacy, their undefined dosages and administration protocols pose challenges for clinical standardization in the form of OIT. Emerging developments include recombinant probiotics engineered to express the specific allergen in a controlled manner inside the gut. However, safety concerns regarding their clinical application remain under active discussion. This review highlights various bioengineering strategies to enhance the probiotic capacity, address safety considerations, and explore future prospects for managing food allergies. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations—2nd Edition)

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