Alimentary Pharmacology & Therapeutics最新文献

{"title":"Letter: Is Enteric Neuropathy Absent in Hypermobility Spectrum Disorders/Hypermobile Ehler–Danlos Syndrome? Authors' Reply","authors":"Kim W. E. Sweerts,&nbsp;Zlatan Mujagic,&nbsp;Daniel Keszthelyi,&nbsp;José M. Conchillo","doi":"10.1111/apt.70157","DOIUrl":"10.1111/apt.70157","url":null,"abstract":"<p>We appreciate the interest and comments of Dr. Green and colleagues on our article about antroduodenal motility in patients with hypermobility spectrum disorders/hypermobile Ehlers–Danlos syndrome (HSD/hEDS) [<span>1, 2</span>].</p><p>They commented on the high frequency of food intolerance in the HSD/hEDS population resulting in a high prevalence of enteral and parenteral feeding, and the possible role of enteric dysmotility regarding this problem. Enteric dysmotility is often thought to be the underlying cause of food intolerance. However, in our study, enteric dysmotility was present less often (but not entirely absent) in the HSD/hEDS group with gastrointestinal symptoms compared to the control group despite the greater need for enteral/parenteral nutrition in the HSD/hEDS group.</p><p>Regarding the duration of antroduodenal manometry (ADM) protocols, we also see the added value of 24-h recordings. However, given the invasive nature and feasibility of 24-h measurements, we also see major challenges. Furthermore, two recent studies showed that shorter ADM studies of 4 or 7.5 h are reliable for evaluation of enteric motility [<span>3, 4</span>].</p><p>Our findings suggest that enteric dysmotility is not the main cause for gastrointestinal complaints in the HSD/hEDS population. A broader view on the pathophysiological mechanism underlying gastrointestinal symptoms in HSD/hEDS patients is necessary. Visceral hypersensitivity should be explored further in this context: it is well described in relation to disorders of gut-brain interaction and contributes significantly to symptom generation in response to normal physiological stimuli, such as food [<span>5</span>]. This phenomenon can be translated to patients with HSD/hEDS, who can exhibit characteristics of central sensitisation and enhanced pain perception, possibly linked to autonomic dysfunction [<span>6</span>]. Additionally, dietary habits and psychological comorbidities including disordered eating must be included in this broader framework because psychiatric problems such as eating disorders are not uncommon within the HSD/hEDS population [<span>7, 8</span>].</p><p>In conclusion, we agree that further research is warranted to elucidate the gastrointestinal manifestations of HSD/hEDS, with particular emphasis on food intolerances. However, we advocate for a more comprehensive approach that addresses gastric and enteric dysmotility but also encompasses factors such as visceral hypersensitivity, autonomic dysfunction, dietary habits and psychological factors.</p><p><b>Kim W. E. Sweerts:</b> writing – original draft. <b>Zlatan Mujagic:</b> writing – review and editing. <b>Daniel Keszthelyi:</b> writing – review and editing. <b>José M. Conchillo:</b> writing – review and editing.</p><p>This article is linked to Sweerts et al. paper. To view this article, visit, https://doi.org/10.1111/apt.18471 and https://doi.org/10.1111/apt.70142.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 11","pages":"1845-1846"},"PeriodicalIF":6.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effectiveness of Medical Therapies for Joint, Skin and Eye Extraintestinal Manifestations in IBD—An Umbrella Review","authors":"Olga M. Nardone,&nbsp;Nurulamin M. Noor,&nbsp;Aniruddh Prabhu,&nbsp;Alessandra Lim,&nbsp;Anirudh Krishnakumar,&nbsp;Abdulaziz Alajmi,&nbsp;Yuhong Yuan,&nbsp;Vipul Jairath,&nbsp;Maria Manuela Estevinho,&nbsp;Virginia Solitano","doi":"10.1111/apt.70181","DOIUrl":"10.1111/apt.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extraintestinal manifestations (EIMs) occur commonly in patients with inflammatory bowel disease (IBD), affecting joints, skin, eyes and other organs, and contributing to morbidity and long-term disability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To synthesise evidence from systematic reviews (SRs) on the effectiveness and safety of medical treatments for IBD EIMs in IBD of joints, skin and eyes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this umbrella review, we searched three databases for relevant SRs published until May 30, 2024. Two independent reviewers performed screening, data extraction and quality appraisal (AMSTAR-2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten, 12 and six SRs, respectively, provided data on medical therapies for articular, dermatological and ocular manifestations. Anti-TNF therapy showed high response rates for axial (59.1%–61.8%) and peripheral arthritis (73.4%–81.2%). The lowest improvement was in patients treated with vedolizumab for joint manifestations. Ustekinumab was effective for arthralgia and psoriatic arthritis, but not for axial spondylarthritis. High heterogeneity of response was reported for anti-TNF, vedolizumab, ustekinumab and tofacitinib (21%–100%) depending on the dermatological manifestation. No SRs evaluated IL-23 p40 antagonists or other oral small molecules. The incidence of new ocular EIMs was 1% for vedolizumab and ustekinumab. Anti-TNF agents were effective for most ocular EIM cases. Ustekinumab improved ocular symptoms in 55%–59%. Safety data were limited, with evidence certainty ranging from moderate to low.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Evidence for medical therapies for joint, skin and eye EIMs in IBD is heterogeneous and of low quality. Further research is needed, including a multidisciplinary approach and novel and practical methods for endpoint evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1854-1871"},"PeriodicalIF":6.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Real-World Effectiveness of Mirikizumab in Ulcerative Colitis—A Valuable but Preliminary Glimpse. Authors' Reply","authors":"Shinichiro Shinzaki,&nbsp;Yasuhiro Takagi,&nbsp;Toshiyuki Sato","doi":"10.1111/apt.70180","DOIUrl":"10.1111/apt.70180","url":null,"abstract":"&lt;p&gt;We thank Drs. Ainsworth and Frimor for their thoughtful editorial comments on our manuscript [&lt;span&gt;1, 2&lt;/span&gt;]. The authors introduced two papers that slightly preceded our report and provided initial insights into the real-world use of mirikizumab. Our study had a broader, more heterogeneous population enabling more detailed analyses as well as subgroup analyses comparing clinical outcomes by prior biologic exposure, including ustekinumab and anti-TNF agents.&lt;/p&gt;&lt;p&gt;In a single-centre report comprising 20 cases [&lt;span&gt;3&lt;/span&gt;], the clinical remission rate (SCCAI &lt; 3) at Week 12 was 83%, which was higher than our 44% (PMS &lt; 2). The difference in the proportion achieving clinical remission from Week 0 to 12 was similar, with 53% (30%–83%) in their study and 40% (4%–44%) in ours. This discrepancy may be due to the inclusion of patients with less severe disease in their study, as 30% were in clinical remission at baseline.&lt;/p&gt;&lt;p&gt;The other report was a single-centre series of 10 patients limited to those with prior exposure to ustekinumab, with 7 achieving clinical remission (CAI ≤ 3) at 3 months [&lt;span&gt;4&lt;/span&gt;]. The rate was also numerically higher than our report (44%), probably because their study included patients with relatively mild disease, with CAI of 5–10 at baseline. Although the clinical activity indices used in each report differ, our study appears to have included patients with more severe disease.&lt;/p&gt;&lt;p&gt;Clinical remission rates at Week 12 were 44% for both ustekinumab-exposed and -naïve patients [&lt;span&gt;2&lt;/span&gt;], suggesting that mirikizumab may retain therapeutic value even after IL-23 pathway inhibition. While these findings are exploratory, they provide a valuable signal for future research regarding optimal biologic sequencing.&lt;/p&gt;&lt;p&gt;We agree with the editorial authors' caution regarding the relatively small sample size. This limitation may have increased the risk of type II error, potentially obscuring meaningful differences in subgroup analyses. Nonetheless, we believe our findings offer clinically relevant context, particularly given the high proportion of biologic-experienced patients. Additionally, we reported significant improvements in objective biomarkers such as CRP and leucine-rich α2-glycoprotein (LRG), a marker not assessed in the LUCENT phase 3 trials [&lt;span&gt;5&lt;/span&gt;] but increasingly recognised in real-world UC monitoring. Although faecal calprotectin was not routinely available in our cohort, reports have shown that serum LRG and faecal calprotectin are comparable in monitoring UC before and after advanced therapy [&lt;span&gt;6, 7&lt;/span&gt;]. Our use of LRG provides complementary inflammatory profiling that deserves further prospective validation.&lt;/p&gt;&lt;p&gt;In conclusion, we emphasise that our report provides detailed and meaningful analyses of real-world mirikizumab use, including patients exposed to both ustekinumab and anti-TNF agents, and patients who received extended induction therapy.&lt;/p&gt;&lt;p&gt;The authors' declarat","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1967-1968"},"PeriodicalIF":6.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Real-World Effectiveness of Mirikizumab in Ulcerative Colitis—A Valuable but Preliminary Glimpse","authors":"Mark A. Ainsworth,&nbsp;Camilla Frimor","doi":"10.1111/apt.70160","DOIUrl":"10.1111/apt.70160","url":null,"abstract":"&lt;p&gt;The therapeutic landscape of ulcerative colitis (UC) is rapidly evolving, driven by biologic and small-molecule agents specifically targeting the inflammatory pathways. Among these, mirikizumab, an anti-IL-23p19 monoclonal antibody, recently gained approval based on pivotal randomised controlled trials (RCTs) demonstrating efficacy in both induction and maintenance phases of therapy [&lt;span&gt;1&lt;/span&gt;]. While RCTs are the benchmark for establishing treatment safety and efficacy, real-world evidence (RWE) provides critical complementary insights into treatment effectiveness, safety, and patient heterogeneity beyond the rigid confines of clinical trials.&lt;/p&gt;&lt;p&gt;In a retrospective multicentre study, Takagi et al. have presented the largest dataset to date, evaluating the real-world effectiveness of mirikizumab in patients with UC across three referral centres [&lt;span&gt;2&lt;/span&gt;]. Although this is not the first study to provide RWE on mirikizumab [&lt;span&gt;3, 4&lt;/span&gt;], its contributions are particularly noteworthy due to its larger sample size. However, the number of patients included in this investigation remains very modest. The investigators evaluated early treatment response at 12 weeks using partial Mayo scores and biochemical markers, alongside safety outcomes. The inclusion of patients previously treated with ustekinumab—who were excluded from the pivotal LUCENT trials [&lt;span&gt;1&lt;/span&gt;]—has enhanced the relevance of the results. Notably, this study represents a pioneering comparison of clinical responses between ustekinumab-naïve and experienced patients, revealing no significant difference in outcomes, thus contributing to a nuanced understanding of biologic sequencing in UC management [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The authors should be recognised for addressing a significant unmet need in post-marketing surveillance, particularly by assessing outcomes in a biologic-experienced population. Their findings complement those of smaller studies on mirikizumab's efficacy in real-world settings [&lt;span&gt;3, 4&lt;/span&gt;]. However, the study has limitations; the small sample size, despite being the largest published to date, may constrain the ability to detect differences in subgroup analyses and increase the risk of type II error. Furthermore, the reliance on C-reactive protein as an inflammatory marker, without considering faecal calprotectin—a more specific UC biomarker—reduces the overall robustness of the efficacy assessment [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Despite these limitations, this early real-world experience is valuable but highlights the need for larger, prospective observational studies that consider biomarker-guided responses, extended follow-ups, and patient-reported outcomes. Such research is essential to refine treatment strategies and address cost-effectiveness, guiding clinicians in the evidence-based sequencing of biologic therapies [&lt;span&gt;7-10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In conclusion, this study represents a meaningful step forward in contextualising mirikizumab's rol","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1965-1966"},"PeriodicalIF":6.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trial: Effect of a 28-Day Low FODMAP Diet on Gastrointestinal Symptoms Associated With Endometriosis (EndoFOD)—A Randomised, Controlled Crossover Feeding Study","authors":"Jane E. Varney,&nbsp;Daniel So,&nbsp;Peter R. Gibson,&nbsp;Dakota Rhys-Jones,&nbsp;Yuet Sang Jimmy Lee,&nbsp;Jane Fisher,&nbsp;Judith S. Moore,&nbsp;Roni Ratner,&nbsp;Mark Morrison,&nbsp;Rebecca E. Burgell,&nbsp;Jane G. Muir","doi":"10.1111/apt.70161","DOIUrl":"10.1111/apt.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastrointestinal symptoms affect most women with endometriosis, but therapeutic interventions are poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To compare the effects of a 28-day low fermentable oligo-, di- and mono-saccharides and polyols (FODMAP) or control diet on gastrointestinal symptom severity in individuals with endometriosis and poorly controlled gastrointestinal symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>In this single-blinded randomised, controlled cross-over feeding trial, we randomised women aged ≥ 18 years to 28 days of either a low FODMAP (&lt; 5 g/day FODMAPs) or control diet (20 g/day FODMAPs), both modelled on Australian Dietary Guidelines, before a ≥ 28-day washout and crossover to the alternate diet. The primary outcome was the proportion of responders defined according to the response in overall gastrointestinal symptoms on a 100-mm visual analogue scale. Secondary outcomes included gastrointestinal symptoms, quality of life and psychological status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 35 women randomised (mean age 31; 95% confidence interval 29, 33 years), 21 (60%) responded to the low FODMAP diet compared with 9 (26%) to the control diet (<i>p</i> = 0.008). In the 4th week of the dietary intervention, overall symptom scores were 35 (21, 42) mm on the low FODMAP diet and 58 (55, 65) mm on the control diet (<i>p</i> &lt; 0.001). Abdominal pain, bloating, stool form and quality of life for both gastrointestinal and endometriosis-associated scales were significantly better for the low FODMAP diet compared with the control diet, but not overall for perceived stress, anxiety or depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The low FODMAP diet ameliorates gastrointestinal symptoms related to endometriosis and improves quality of life. Confirmation of these findings in a real-world setting is required.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000153819).</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1889-1903"},"PeriodicalIF":6.6,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenofovir Alafenamide Therapy Throughout Pregnancy in Mothers With Hepatitis B","authors":"Xingfei Pan, Liyang Zhou, Jing Hu, Panpan Zhai, Xueting Ou, Fang He, Calvin Q. Pan","doi":"10.1111/apt.70173","DOIUrl":"https://doi.org/10.1111/apt.70173","url":null,"abstract":"BackgroundMothers with chronic hepatitis B and advanced fibrosis may require antiviral therapy throughout pregnancy. Current guidelines recommend tenofovir disoproxil fumarate (TDF), which is unsuitable for mothers at risk of renal dysfunction or decreased bone mineral density.AimsThis study aimed to evaluate the safety of tenofovir alafenamide (TAF) therapy during pregnancy.MethodsMothers with chronic hepatitis B treated with TAF or no therapy were retrospectively enrolled and categorised into three groups: (A) TAF‐first trimester, (B) TAF‐late trimester and (C) no treatment. Propensity score matching was applied to create comparable groups. Primary assessments included serious adverse events up to postpartum week 28, while secondary assessments examined predictors of such events and vertical transmission rates.ResultsAmong 284 mothers, 160 were selected. No significant differences were observed in foetal loss, low birth weight, preterm delivery or congenital abnormalities between groups A and B, or between groups A and C. Other adverse events were similar across groups, except for a higher incidence of gestational diabetes in the TAF‐first trimester group. In vitro fertilisation was identified as the sole predictor of serious events. No infants were reported with hepatitis B virus infection at 28 weeks postpartum.ConclusionsThis study suggests that TAF treatment throughout pregnancy is safe for mothers with chronic hepatitis B and their infants. TAF therapy represents a viable treatment option for these mothers.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"74 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes Following Withdrawal of Anti-Tumour Necrosis Factor Treatment in Inflammatory Bowel Disease Patients in Remission: The Exit Long-Term Study of GETECCU","authors":"María José Casanova, Cristina Rubín de Célix, Sabino Riestra, Alfredo J. Lucendo, José Manuel Benítez, Mercè Navarro-Llavat, Jesús Barrio, Víctor J. Morales-Alvarado, Montserrat Rivero, David Busquets, Eduardo Leo-Carnerero, Oscar Nantes-Castillejo, Pablo Navarro, Manuel Van Domselaar, Ana Gutiérrez-Casbas, Inmaculada Alonso-Abreu, Manuel Barreiro-de Acosta, Luis Fernández-Salazar, Marisa Iborra, María Dolores Martín-Arranz, Natalia García-Morales, Jordi Guardiola, Abdel Bouhmidi-Assakali, María Esteve, Carmen Muñoz-Villafranca, Iago Rodríguez-Lago, Daniel Ceballos, Iván Guerra, Miriam Mañosa, Ignacio Marín-Jiménez, Isabel Vera-Mendoza, Ana Garre, María Chaparro, Javier P. Gisbert","doi":"10.1111/apt.70172","DOIUrl":"https://doi.org/10.1111/apt.70172","url":null,"abstract":"The EXIT trial found no difference in sustained remission at 12 months between inflammatory bowel disease (IBD) patients in remission who withdrew anti-TNF therapy [withdrawal arm (WA)] and those who maintained treatment [maintenance arm (MA)].","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Clarifying the Synergistic Mechanisms of Mediterranean Diet and Time-Restricted Feeding in MASLD Management—Authors' Reply","authors":"Sofia Tsitsou,&nbsp;Magdalini Adamantou,&nbsp;Triada Bali,&nbsp;Aristi Saridaki,&nbsp;Kalliopi-Anna Poulia,&nbsp;Dimitrios S. Karagiannakis,&nbsp;Emilia Papakonstantinou,&nbsp;Evangelos Cholongitas","doi":"10.1111/apt.70178","DOIUrl":"10.1111/apt.70178","url":null,"abstract":"<p>We sincerely thank Drs. Zhu and Zhou [<span>1</span>] for their thoughtful comments on our recent randomised study examining the effects of a 12-week Mediterranean-type time-restricted feeding (TRF) protocol in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [<span>2</span>].</p><p>Our study is distinguished by the use of a hypocaloric Mediterranean diet as the control group, which has emerged as the gold standard for MASLD dietary management. This aligns with current recommendations emphasising lifestyle changes and a target weight loss of over 5% of initial body weight as primary treatment goals [<span>3, 4</span>]. Previous studies have shown that ad libitum TRF can lead to modest weight loss (1%–4%), while greater, clinically significant reductions typically require caloric restriction [<span>5</span>]. Therefore, combining TRF with a structured hypocaloric approach offers a promising avenue, as demonstrated by improvements in key metabolic parameters in our trial and others [<span>2, 6</span>].</p><p>We appreciate the pertinent questions raised regarding the underlying mechanisms and impact in specific sub-groups of such dietary interventions [<span>1</span>]. As pointed out in our original article [<span>2</span>], further research is needed to explore these complex interactions. Although a single clinical trial cannot address all knowledge gaps, we believe that our study lays the groundwork for future investigations in this scientific area. Ongoing planned analyses from our clinical trial may give insight into the field of circadian rhythms.</p><p>The authors' declarations of personal and financial interests are unchanged from those in the original article [<span>2</span>].</p><p><b>Sofia Tsitsou:</b> writing – original draft, investigation, methodology, data curation. <b>Magdalini Adamantou:</b> writing – original draft, data curation, investigation. <b>Triada Bali:</b> investigation, data curation. <b>Aristi Saridaki:</b> data curation, investigation. <b>Kalliopi-Anna Poulia:</b> methodology. <b>Dimitrios S. Karagiannakis:</b> methodology. <b>Emilia Papakonstantinou:</b> writing – review and editing, methodology. <b>Evangelos Cholongitas:</b> conceptualization, investigation, methodology, writing – review and editing, project administration, supervision, visualization, writing – original draft.</p><p>This article is linked to Tsitsou et al. paper. To view this article, visit, https://doi.org/10.1111/apt.70044 and https://doi.org/10.1111/apt.70154.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1983-1984"},"PeriodicalIF":6.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Inflammatory Bowel Disease and Dietary Emulsifiers—A Conundrum That Continues","authors":"Stephanie Gold,&nbsp;Natasha Haskey,&nbsp;Maitreyi Raman","doi":"10.1111/apt.70112","DOIUrl":"10.1111/apt.70112","url":null,"abstract":"&lt;p&gt;The impact of ultra-processed foods (UPFs) on inflammatory bowel disease (IBD) pathogenesis is increasingly recognised [&lt;span&gt;1-3&lt;/span&gt;]. Clinical and preclinical studies link UPFs, including dietary emulsifiers, to dysbiosis, mucous layer disruption and immune activation [&lt;span&gt;1, 2&lt;/span&gt;]. Since the increasing consumption of processed foods has been linked to increased incidence and prevalence of chronic disease, including IBD, the influence of UPF consumption on IBD-related outcomes is of major interest [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Fitzpatrick et al. [&lt;span&gt;4&lt;/span&gt;] conducted a double-blinded randomised controlled trial in patients with active ileal Crohn's disease. Nineteen participants received either a high emulsifier diet (HED) or low emulsifier diet (LED) for 4 weeks. There were no significant differences in improvement in clinical disease activity, intestinal ultrasound findings or quality of life between the two groups. The authors concluded that the findings did not support the current recommendations for patients to avoid dietary emulsifiers.&lt;/p&gt;&lt;p&gt;Controlled feeding studies, such as this [&lt;span&gt;4&lt;/span&gt;], provide an opportunity to isolate and assess the impact of specific food components. Notable strengths of this study included its blinded, randomised design; carefully formulated dietary interventions; and integration of clinical biomarkers and patient-reported outcomes to evaluate effectiveness.&lt;/p&gt;&lt;p&gt;The study also had several limitations. The small sample and high dropout rate (&gt; 20%, with 10 patients on HED and nine on LED) limit the ability to draw definitive conclusions about the impact of emulsifiers versus other dietary components, or disease activity on gastrointestinal symptoms. Moreover, the short dietary intervention period may not have been long enough to see the full impact of the emulsifiers, especially in this small cohort.&lt;/p&gt;&lt;p&gt;Moreover, the study lacked formal assessment of dietary quality and other potential confounding dietary components. While the diets followed ‘healthy eating guidelines’, standardised dietary assessment tools such as the Healthy Eating Index or the Mediterranean Diet Score could have identified differences beyond emulsifier content [&lt;span&gt;5-9&lt;/span&gt;]. Emulsifier quantification was also limited with no distinction between naturally occurring and synthetic emulsifiers (e.g., polysorbate 80 vs. egg yolks), despite their potential for differing effects on the microbiome [&lt;span&gt;10&lt;/span&gt;]. Furthermore, NOVA classification of the actual rather than recommended food intake would have provided a more accurate diet assessment.&lt;/p&gt;&lt;p&gt;Despite the reported high adherence to the diets based on food diaries, it remains unclear how many patients were fully compliant during the intervention. Assessing dietary compliance is crucial, particularly in a study with so few participants. Additionally, while the diets were designed to meet energy requirements, all patients experienced weight loss, which may be s","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1961-1962"},"PeriodicalIF":6.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Clarifying the Synergistic Mechanisms of Mediterranean Diet and Time-Restricted Feeding in MASLD Management","authors":"Weixiong Zhu,&nbsp;Wence Zhou","doi":"10.1111/apt.70154","DOIUrl":"10.1111/apt.70154","url":null,"abstract":"<p>The CHRONO-NAFLD trial by Tsitsou et al. [<span>1</span>] provides valuable insights into combining Mediterranean diet (MD) and time-restricted feeding (TRF) for metabolic dysfunction-associated steatotic liver disease (MASLD). While the study demonstrates comparable weight loss across groups and superior glycemic benefits with early TRF, three critical questions warrant further discussion to contextualise these findings.</p><p>First, the caloric restriction confounder limits mechanistic interpretation. All groups followed a hypocaloric MD (−500 kcal/day), which itself drives weight loss and metabolic improvements. Prior studies show that TRF's benefits on hepatic steatosis and insulin sensitivity are most pronounced in ad libitum feeding models [<span>2</span>]. By superimposing TRF on caloric restriction, the independent effects of circadian alignment may be obscured. Future trials should isolate TRF's impact by comparing isocaloric TRF vs. non-TRF arms.</p><p>Second, the lack of circadian biomarker data (e.g., melatonin, cortisol rhythms) leaves a key knowledge gap. TRF's efficacy likely depends on synchronising food intake with endogenous circadian clocks regulating hepatic metabolism [<span>3</span>]. The differential glycemic outcomes between eTRF and lTRF groups suggest timing-specific effects on insulin signalling pathways, potentially mediated by clock gene modulation (e.g., BMAL1, PER2). Including circadian phase assessments would clarify whether clinical benefits correlate with restored rhythmicity.</p><p>Lastly, heterogeneity in baseline metabolic dysfunction (e.g., 34% with diabetes, 61% with metabolic syndrome) may have diluted intervention effects. Subgroup analyses stratified by glycemic status or fibrosis severity could identify patients most likely to benefit from TRF-MD synergy. For instance, prediabetic patients showed greater HbA1c reductions in eTRF (−0.3%), aligning with evidence that circadian interventions preferentially improve early dysmetabolism [<span>4</span>].</p><p>While this trial confirms MD's foundational role in MASLD, unravelling the chronobiological mechanisms of TRF and personalising its application remain critical next steps.</p><p><b>Weixiong Zhu:</b> conceptualization, writing – original draft, investigation. <b>Wence Zhou:</b> writing – review and editing, funding acquisition.</p><p>This article is linked to Tsitsou et al papers. To view these articles, visit https://doi.org/10.1111/apt.70044 and https://doi.org/10.1111/apt.70178.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1981-1982"},"PeriodicalIF":6.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}