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Feasibility, Safety, and Preliminary Efficacy of Very Low-Volume Interval Training in Advanced Cancer Patients.
Reljic, D, Herrmann, HJ, Jakobs, B, Dieterich, W, Mougiakakos, D, Neurath, MF, Zopf, Y
Medicine and science in sports and exercise. 2022;(11):1817-1830
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Abstract
PURPOSE High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (CRF) and health-related outcomes in various chronic diseases, including cancer. However, data on feasibility and efficacy of HIIT in advanced cancer patients are still sparse, presumably because of safety concerns, like suspected immunosuppression after vigorous exercise. This randomized, sham-intervention controlled study aimed to investigate feasibility, safety, and preliminary efficacy of very low-volume HIIT (LOW-HIIT) in advanced cancer patients. METHODS Twenty-seven patients (55.4 ± 13.2 yr) with different advanced cancers (Union for International Cancer Control [UICC] III/IV) were randomly allocated to LOW-HIIT ( n = 13), consisting of 5 × 1 min cycle ergometer intervals (14 min per session total duration) at 80% to 95% HR peak (two sessions per week for 12 wk), or a sham intervention ( n = 14) performing light physical mobilization exercises (SHAM). Primary outcomes were attrition and attendance rates, with values of ≤25% and ≥80%, respectively, considered acceptable. Secondary outcomes were safety, protocol fidelity, physiological (including CRF measures) and patient-reported outcomes (including fatigue and quality of life). RESULTS One of 13 patients (8%) receiving LOW-HIIT dropped out. Mean attendance rate was ~93%. The prescribed minimum exercise intensity was consistently reached by all patients. Low-volume HIIT was well tolerated and not associated with any serious adverse event nor with increased infection susceptibility. There were no biochemical signs of acute immunosuppression after LOW-HIIT. Contrarily, differentiation and degranulation of natural killer cells was acutely increased postexercise. Low-volume HIIT improved CRF measures including peak oxygen uptake, self-reported fatigue, physical, and social functioning. No significant changes occurred in the SHAM group. CONCLUSIONS Low-volume HIIT can be regarded as feasible and safe in advanced cancer patients. Our preliminary data indicate favorable acute effects on NK-cells and beneficial chronic adaptations in CRF, fatigue, and aspects of quality of life.
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"HIIT the Inflammation": Comparative Effects of Low-Volume Interval Training and Resistance Exercises on Inflammatory Indices in Obese Metabolic Syndrome Patients Undergoing Caloric Restriction.
Reljic, D, Dieterich, W, Herrmann, HJ, Neurath, MF, Zopf, Y
Nutrients. 2022;(10)
Abstract
Exercise is a cornerstone in metabolic syndrome (MetS) treatment. However, the effects of low-volume exercise modalities on MetS-associated low-grade inflammation are unclear. A total of 106 MetS patients (53.7 ± 11.4 years) were randomized to low-volume high-intensity interval training (LOW-HIIT, 14 min/session), single-set resistance training (1-RT, ~15 min/session), whole-body electromyostimulation (WB-EMS, 20 min/session), three-set resistance training (3-RT, ~50 min/session), each performed 2 ×/week for 12 weeks, or a control group (CON). All groups received nutritional counseling for weight loss. Inflammatory and cardiometabolic indices were analyzed pre- and post-intervention. All groups significantly reduced body weight by an average of 3.6%. Only LOW-HIIT reduced C-reactive protein (CRP) (−1.6 mg/L, p = 0.001) and interleukin-6 (−1.1 pg/mL, p = 0.020). High-sensitivity CRP and lipopolysaccharide-binding protein decreased following LOW-HIIT (−1.4 mg/L, p = 0.001 and −2.1 ng/mL, p = 0.004) and 3-RT (−0.6 mg/L, p = 0.044 and −2.0 ng/mL, p < 0.001). MetS severity score improved with LOW-HIIT (−1.8 units, p < 0.001), 1-RT (−1.6 units, p = 0.005), and 3-RT (−2.3 units, p < 0.001). Despite similar effects on body weight, low-volume exercise modalities have different impact on inflammatory and cardiometabolic outcomes in MetS patients. LOW-HIIT has superior efficacy for improving inflammation compared to 1-RT and WB-EMS. Resistance-based exercise appears to require a higher volume to promote beneficial impact on inflammation.
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An algorithm for differentiating food antigen-related gastrointestinal symptoms.
Rostami, K, Bold, J, Ismail Ali, J, Parr, A, Dieterich, W, Zopf, Y, Htoo, A, Rostami-Nejad, M, Danciu, M
Gastroenterology and hepatology from bed to bench. 2021;14(1):8-16
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Irritable bowel syndrome (IBS) is a collection of gastrointestinal symptoms. Due to multiple etiologies, the pathogenesis of IBS is poorly understood. The aim of this audit was to assess the outcomes achieved using a lactose and gluten-free diet clinical intervention in patients traditionally diagnosed with IBS. This study was an audit of outcomes from the records of 149 patients presenting with IBS symptoms at secondary and tertiary Gastroenterology outpatients in two UK hospitals. This audit has demonstrated that more than 70% of patients presenting with IBS symptoms improved by following a diet eliminating lactose and gluten containing grains (improvement for >30% in their symptoms). The success of the elimination diet did not seem to be correlated with the body mass index (BMI). The best outcome was recorded in patients with normal BMI and also in the overweight group. Patients with higher BMI >30 or low below 18 also responded well to nutrition therapy. In conclusion, multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
Abstract
AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
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Food Intolerance of Unknown Origin: Caused by Mucosal Inflammation? A Pilot Study.
Dieterich, W, Tietz, E, Kohl, M, Konturek, PC, Rath, T, Neurath, MF, Zopf, Y
Clinical and translational gastroenterology. 2021;(2):e00312
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Abstract
INTRODUCTION The prevalence of patients with food intolerance (FI) has increased significantly. Immunoglobulin (Ig)E-mediated food allergies (FAs) are detected by determining IgE antibodies and skin prick test. Carbohydrate malabsorptions are clarified with breath tests. However, these diagnostic measures cannot capture all intolerances and have limitations in case of gut-mediated FI. The aims of this pilot study were to evaluate different methods to determine intestinal mucosal IgE in patients with FA and to characterize the intestinal mucosa in patients with FI of unknown origin (FH). METHODS Patients with FA and FH were compared with healthy controls. To determine the IgE antibodies and the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ of the intestinal mucosal, a lavage was performed as part of an ileocolonoscopy and samples were taken using the cytobrush and biopsy forceps. In a subgroup, mucosal samples were also taken from the duodenum. RESULTS Data in homogenates of intestinal mucosal samples yielded the highest sensitivity for IgE antibody titers compared with lavage and cytobrush. Patients with FA presented increased intestinal TNF-α and low IFN-γ values. This was in contrast to FH patients, who showed low intestinal IgE antibodies and TNF-α levels, but increased IFN-γ values. DISCUSSION The determination of IgE antibodies to diagnose intestinal IgE-mediated FA is most reliable in intestinal mucosal samples. Increased TNF-α and low IFN-γ levels in patients with FA characterize an allergic reaction. Decreased TNF-α and increased IFN-γ levels in patients with FH indicate an inflammation-related intolerance reaction (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A520).
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Intestinal ex vivo organoid culture reveals altered programmed crypt stem cells in patients with celiac disease.
Dieterich, W, Neurath, MF, Zopf, Y
Scientific reports. 2020;(1):3535
Abstract
The ex vivo generation of gastrointestinal organoids from crypt stem cells opens up the possibility of new research approaches investigating gastrointestinal diseases. We used this technology to study differences between healthy controls and patients with celiac disease (CD). We noticed distinct dissimilarities in the phenotypes of organoids between our study groups and found considerable variations in their gene expression. Extracellular matrix genes involved in epithelial-mesenchymal transition are expressed most differently. In addition, we demonstrated epigenetic modifications that might be responsible for the different organoid gene expression thus accounting for a deranged crypt/villus axis development in CD. The organoids have proven valuable to demonstrate fundamental differences in duodenal derived organoids between healthy controls and patients with CD and thus are a suitable tool to gain new insights in pathogenesis of CD.
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Microbiota in the Gastrointestinal Tract.
Dieterich, W, Schink, M, Zopf, Y
Medical sciences (Basel, Switzerland). 2018;(4)
Abstract
Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and varying environmental conditions, e.g., diets, antigen exposure, infections, or medication, as well as genetics, age, or hygiene factors, strongly influence the bacterial community. A fine interaction between the host and microbiota determines the outcome of health or disease. The gut immune system is constantly challenged to distinguish between commensal non-invasive bacteria and potential pathogens. Goblet cells produce mucins that prevent most gut bacteria from penetrating through intestinal epithelial barrier, and Paneth cells are the main supplier of anti-microbial defensins. Gut epithelial and immune cells recognize bacteria via surface markers and they initiate an adequate immune answer. A dysbiosis is noticed in several diseases, but the crucial role in pathogenesis has to be proven. Prebiotics or probiotics are discussed as valuable tools to preserve or restore a healthy gut community.
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Dietary Effects on Microbiota-New Trends with Gluten-Free or Paleo Diet.
Zopf, Y, Reljic, D, Dieterich, W
Medical sciences (Basel, Switzerland). 2018;(4)
Abstract
A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, largely associated with dramatic changes in food consumption trends and main nutrients. A major response to food intolerances has been the adoption of new dietary trends involving the reduction or exclusion of specific food ingredients. Especially gluten-containing, but also gluten-free cereals are in the cross-fire. Supporters of the gluten-free diet argue that gluten triggers inflammation and related diseases, while followers of the Paleo diet drastically impeach all cereals as dangerous for human health. To date, no controlled studies support or reject a positive health effect of a gluten-free or cereal-free diet. Future large-scale studies need to evaluate the effect of gluten-containing and gluten-free cereals and the various diets on human health, inflammatory parameters, clinical symptoms, and the gut microbiota (including the bacteria, fungi, and viruses). Dietary-associated changes in compositional and functional microbiota traits should be correlated with the health status for the future development of dietary recommendations and potential clinical interventions.
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The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update.
Catassi, C, Alaedini, A, Bojarski, C, Bonaz, B, Bouma, G, Carroccio, A, Castillejo, G, De Magistris, L, Dieterich, W, Di Liberto, D, et al
Nutrients. 2017;(11)
Abstract
Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.
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Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.
Catassi, C, Elli, L, Bonaz, B, Bouma, G, Carroccio, A, Castillejo, G, Cellier, C, Cristofori, F, de Magistris, L, Dolinsek, J, et al
Nutrients. 2015;(6):4966-77
Abstract
Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.
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[Non-celiac disease non-wheat allergy wheat sensitivity].
Zopf, Y, Dieterich, W
Deutsche medizinische Wochenschrift (1946). 2015;(22):1683-7
Abstract
Non-celiac non-wheat allergy wheat sensitivity is regarded as discrete glutensensitivity diagnosed after the exclusion of celiac disease and wheat allergy. Due to the absence of reliable biomarkers no exact prevalence rates are known and estimations range between 0,5-6 %. Soon after ingestion of wheat, patients complain of intestinal symptoms mainly bloating, abdominal pain, diarrhea or nausea which improve fast under glutenfree diet. Often extraintestinal manifestation as tiredness, muscle or joint pain, headache and depression are reported. Actually, there are no serological markers and no intestinal mucosal damage was found in patients. The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers. In addition, the involvement of the intestinal microbiome in pathology of glutensensitivity must be considered.