Luxembourgish Fiber Cohort
Fjalë kyçe
Abstrakt
Përshkrim
Industrialized nations tend to consume less dietary fiber and, in many nations with a Western-style diet, average consumption is half the recommended daily intake of 25-38 g/day. Dietary fiber is an important component of a healthy diet because it increases fecal bulking and laxation, lowers cholesterol and regulates levels of blood glucose. The connection between low fiber-intake and disease may rest with the gut microbiota, the trillions of commensal microorganisms that inhabit the gastrointestinal tract. Bacteria found in the gut are responsible for an array of functions that support human health, including conversion of host-indigestible fibers into short chain fatty acids (SCFAs), which provide energy for colonic cells, support mucus production, and modulate the immune system (Martens et al., 2018, Nat Rev).
The investigators have recently investigated the effects of a fiber-free diet in a gnotobiotic mouse model with a 14-member synthetic microbial community showing that mucus-degrading bacteria outcompete fiber-degrading bacteria, causing degradation of the colonic mucus layer (Desai et al., 2016, Cell). One member of this synthetic community, Akkermansia muciniphila, is a commensal bacterium found at 1-4% relative abundance in the human gut and feeds specifically on the host-secreted mucins (Belzer and de Vos, 2012, The ISME Journal). However, this bacterium is significantly enriched in the gut of patients with multiple sclerosis and colorectal cancer, suggesting that its mucolytic capabilities may play a role in these diseases (Weir et al., 2013, PLoS One; Jangi et al., 2016, Nat Commun). A microbial shift toward enrichment of mucolytic bacteria could be an important precursor to gut-linked diseases. While observational studies have identified a lower risk of irritable bowel diseases (IBD) in people who consume diets high in fiber, fruits, and vegetables (Hou et al., 2011, Am J Gastroenterol), no study has explicitly investigated the effects of fiber on the functional capacity of the human gut microbiome in the context of effects on the mucus-degrading microbiome. Based on our published work in mice, for the current project, the investigators hypothesize that deficiency of dietary fiber in humans promotes increased activities of mucus-degrading bacteria, thereby reducing the mucus lining in the intestine. The investigators request pump priming to initiate this pilot project, as it will generate foundational datasets to inform numerous follow-up studies.
Thus, the current project seeks to translate findings from mouse models to humans, using a crossover study among healthy adults. Participants will be randomly assigned to a first dietary intervention that is low or high in fiber and then, following a washout period intended to reverse any compositional changes, switched to the second diet type. The diets will be evaluated by a nutritionist to ensure that they differ in fiber content, but are comparable in terms of caloric and macronutrient content. The targeted amount of dietary fiber intake from the high-fiber test meals will be around 30 g/d more than the low-fiber diet. In addition to dietary records, the investigators will administer questionnaires, obtain basic clinical measures (blood pressure, weight, height, waist/thigh circumference), collect blood samples for immunological assays and collect stool samples before and at the end of each diet intervention for sequencing and functional profiling of bacterial communities.
The investigators will recruit healthy volunteers to participate in a 2x2 crossover design controlled-diet study. After statistical consultation, the investigators conclude that the investigators require a sample size of n=17 in each sequence group (a total sample size of N=34) to have 90% power to detect a -0.5 difference in means for alpha diversity (Shannon index, based on comparable dataset from David et al., 2014, Nature) under the two diet conditions. Thus, in case of dropouts, the investigators have decided to enroll a total of N=40 participants in the study. Volunteers who meet all inclusion and exclusion criteria will be randomly assigned to a high- or low-fiber diet intervention and then, after a week-long washout period, will receive the second diet type. High and low fiber meals containing a variety of fiber types will be served to participants at a designated drop-off site (home or workplace) for one week in order to decrease variance in fiber intake, increase adherence to the diet, and maximize knowledge of the nutritional content in participants' diet. Nutritionally balanced dietary interventions are designed by a qualified dietitian at SERVIOR "Repas sur roues" catering service in conjunction with the LIH study team. Participants on both diet interventions will be given multivitamin supplements in order to further ensure they receive essential vitamins and minerals.
At the baseline visit, our team will work with nurses from the Clinical and Epidemiological Investigation Center (CIEC, headed by Dr. Manon Gantenbein) to collect demographic data, anthropometry, early life history, family medical history, detailed dietary patterns, and biological samples (blood, urine, and stool). Participants will use the MyFitnessPal app to log their diet throughout the study, except for foods or beverages provided during the dietary interventions. After each intervention period, a week-long washout period will be employed to reverse any changes that occurred due to the diet.
Mid-way through each intervention and washout period, the investigators will administer a brief survey containing questions relevant to our research objective. At each of these visits, CIEC nurses will collect biological samples and anthropometric measures. Participants will also be asked to drop off a stool sample for the next two days. All participant data will be pseudonymized when exported from Research Electronic Data Capture application (REDCap) for analysis and will be handled in accordance with the General Data Protection Regulation (GDPR). The study will be submitted for ethical approval by the Ministry of Health and for review by CNER before being opened for recruitment as early as March 2020.
Datat
| Verifikuar së fundmi: | 03/31/2020 |
| Paraqitur së pari: | 02/25/2020 |
| Regjistrimi i vlerësuar u dorëzua: | 04/14/2020 |
| Postuar së pari: | 04/19/2020 |
| Përditësimi i fundit i paraqitur: | 04/14/2020 |
| Përditësimi i fundit i postuar: | 04/19/2020 |
| Data e fillimit të studimit aktual: | 05/31/2020 |
| Data e vlerësuar e përfundimit primar: | 08/31/2020 |
| Data e vlerësimit të përfundimit të studimit: | 12/31/2024 |
Gjendja ose sëmundja
Ndërhyrja / trajtimi
Dietary Supplement: High Fiber Diet Intervention
Dietary Supplement: Low Fiber Diet Intervention
Faza
Grupet e krahëve
| Krah | Ndërhyrja / trajtimi |
|---|---|
| Experimental: High to Low Fiber Diet Intervention Participants receive the high fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the low fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes. | |
| Experimental: Low to High Fiber Diet Intervention Participants receive the low fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the high fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes. |
Kriteret e pranimit
| Moshat e pranueshme për studim | 18 Years Për të 18 Years |
| Gjinitë e pranueshme për studim | All |
| Pranon Vullnetarë të Shëndetshëm | po |
| Kriteret | Inclusion Criteria: 1. Male or female: a. The investigators will aim for a 50:50 male:female ratio, at most 40:60. Therefore, given a sample size of N=40, if 24 eligible participants are exceed for one gender, the investigators will proceed with recruitment only for members of the underrepresented gender. 2. Between 18 and 35 years of age (expand to 55 if needed) 3. BMI between 18.5 ≥ BMI > 25 kg/m2 (expand to 30 if needed) 4. Born in Europe 5. Current resident of Luxembourg City or Esch-sur-Alzette (expand to nearby communes if needed) 6. Own a smartphone with access to Android or Apple Store applications Exclusion Criteria: 1. Following a specific diet or subject to dietary restrictions for any reason 2. "Vigorous" physical activity level based on the International Physical Activity Questionnaire - Short Form (IPAQ-SF) criteria 3. Antibiotics usage within the past 3 months 4. Probiotics usage within the past 1 month 5. Laxatives usage within the past 1 month 6. Other regular medication usage (e.g. ibuprofen, warfarin) 7. Current or former smoker 8. Gastrointestinal disorder (e.g. ulcerative colitis, Crohn's disease) diagnosis 9. History of gastrointestinal surgery (excluding appendectomy) 10. Metabolic disorder diagnosis or predisposition (determined by blood test at eligibility screen) 1. Prediabetes: fasting glucose 100-125 mg/dL (6.1-7.0 mmol/L) and/or drug treatment of elevated glucose (8) 2. Diabetes: fasting glucose ≥126 mg/dL (7.0 mmol/L) and/or drug treatment of elevated glucose and/or previously diagnosed type 1 or type 2 diabetes (8) 3. Hypertriglyceridaemia: fasting triglycerides ≥1.7 mmol/L (≥150 mg/dL) and/or drug treatment for elevated triglycerides (9) 4. Hypercholesterolaemia: Fasting High-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (< 1.0 mmol/L) in men and < 45 mg/dL (< 1.2mmol/L) in women and/or drug treatment for reduced HDL-C (9) 5. Hypertension: Systolic BP ≥130 and/or diastolic BP ≥80 mm Hg and/or drug treatment of previously diagnosed hypertension (10) 11. Cancer (any type) diagnosis (note that a history of cancer that has been in remission for >3 years may still be considered eligible) 12. Immunodeficiency disorder (e.g. HIV) or autoimmune disorder (e.g. rheumatoid arthritis, lupus) diagnosis 13. Neurological disorder (e.g. advanced dementia, diagnosed major depressive disorder or generalized anxiety disorder) 14. Coagulation problems (e.g. hemophilia) or anemia impacting ability to participate in blood draw 15. Circulatory disorder (e.g. ischemic heart diseases or history of stroke) 16. Currently pregnant or lactating (breastfeeding) 17. Vacation planned during study period 18. Moving out of Luxembourg during the study period 19. Potential conflict of interest: involved in study design, administration, data analysis, or publication of findings or belonging to the lab group of the study's principal investigators |
Rezultati
Masat Kryesore të Rezultateve
1. Change in gut microbiota composition across study periods [through study completion, an average of 1 month]
Masat dytësore të rezultateve
1. Change in gut microbiota CAZyme abundance across study periods [through study completion, an average of 1 month]
2. Change in gut microbiota mucolytic enzyme activity across study periods [through study completion, an average of 1 month]
Masat e tjera të rezultateve
1. Change in fecal acetate levels across study periods [through study completion, an average of 1 month]
2. Change in fecal propionate levels across study periods [through study completion, an average of 1 month]
3. Change in fecal butyrate levels across study periods [through study completion, an average of 1 month]
4. Change in CyTOF immune profiles across study periods [through study completion, an average of 1 month]
5. Change in CRP across study periods [through study completion, an average of 1 month]
6. Change in LCN2 across study periods [through study completion, an average of 1 month]
7. Change in calprotectin across study periods [through study completion, an average of 1 month]
8. Change in fasting glucose level across study periods [through study completion, an average of 1 month]
