Healthy Volunteers Clinical Trial
— Lux-FiCoOfficial title:
From Mouse to Man: Translating Findings in Mouse Study Into a Human Cohort (Luxembourgish Fiber Cohort: Lux-FiCo)
Verified date | December 2022 |
Source | Luxembourg Institute of Health |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Many human populations across the world are deficient in the intake of dietary fiber. This decline in fiber consumption parallels an increase in prevalence of a multitude of diseases (e.g. colorectal cancer, multiple sclerosis). A possible link for this association between dietary changes and the diseases could rest in the trillions of commensal gut microbes that digest dietary fibers, provide energy for colonic cells, and modulate the immune system. However, the molecular mechanisms that link fiber deficiency via the activities of the gut microbiome to various diseases have been poorly understood. The investigators previously showed that, in a mouse model with a defined human gut microbiota, removal of fiber from the diet favors proliferation of bacteria that degrade the gut's protective mucus lining. In the proposed project, the investigators aim to translate our findings from mouse studies to humans using a 2x2 crossover study among healthy adults. Forty participants will be randomly assigned to a low- or high-fiber dietary intervention and then, following a washout period to reverse any changes, switched to the other diet type. By employing longitudinal sampling of stool collections, the investigators envision that participants will exhibit increased abundance and activities of mucolytic bacteria when fed a low-fiber diet. The unique selling point of the proposed study involves setting up high-throughput culture collections of mucus-degrading bacteria, whose abundances and activities will be investigated by sequencing and enzymatic assays in stool. Additionally, the investigators will measure inflammatory markers in blood using CyTOF to assess whether short-term fiber deficiency exerts detectable changes in the host immune function. Thus, the proposed dietary intervention clinical trial will help elucidate the role of fiber deficiency in various chronic diseases.
Status | Completed |
Enrollment | 30 |
Est. completion date | December 5, 2022 |
Est. primary completion date | December 5, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Luxembourg | Luxembourg Institute of Health | Esch-sur-Alzette | |
Luxembourg | Luxembourg Institute of Health | Strassen |
Lead Sponsor | Collaborator |
---|---|
Luxembourg Institute of Health | Centre Hospitalier du Luxembourg, Integrated Biobank of Luxembourg, Luxembourg Centre for Systems Biomedicine |
Luxembourg,
Belzer C, de Vos WM. Microbes inside--from diversity to function: the case of Akkermansia. ISME J. 2012 Aug;6(8):1449-58. doi: 10.1038/ismej.2012.6. Epub 2012 Mar 22. — View Citation
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11. — View Citation
Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Nunez G, Martens EC. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043. — View Citation
Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol. 2011 Apr;106(4):563-73. doi: 10.1038/ajg.2011.44. — View Citation
Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, Patel B, Mazzola MA, Liu S, Glanz BL, Cook S, Tankou S, Stuart F, Melo K, Nejad P, Smith K, Topcuolu BD, Holden J, Kivisakk P, Chitnis T, De Jager PL, Quintana FJ, Gerber GK, Bry L, Weiner HL. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016 Jun 28;7:12015. doi: 10.1038/ncomms12015. — View Citation
Martens EC, Neumann M, Desai MS. Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier. Nat Rev Microbiol. 2018 Aug;16(8):457-470. doi: 10.1038/s41579-018-0036-x. — View Citation
Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013 Aug 6;8(8):e70803. doi: 10.1371/journal.pone.0070803. Print 2013. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in fecal acetate levels across study periods | Acetate concentrations by mass spectrophotometry over last 3 days of each study period. | through study completion, an average of 1 month | |
Other | Change in fecal propionate levels across study periods | Propionate concentrations by mass spectrophotometry over last 3 days of each study period. | through study completion, an average of 1 month | |
Other | Change in fecal butyrate levels across study periods | Butyrate concentrations by mass spectrophotometry over last 3 days of each study period. | through study completion, an average of 1 month | |
Other | Change in CyTOF immune profiles across study periods | Changes to the immune cell populations, profiled using Time of Flight Mass Cytometry (CyTOF). | through study completion, an average of 1 month | |
Other | Change in CRP across study periods | Changes to levels of C reactive protein (CRP), a general inflammatory marker, assayed using ELISA kits. | through study completion, an average of 1 month | |
Other | Change in LCN2 across study periods | Changes to levels of lipocalin-2 (LCN2), a general inflammatory marker, assayed using ELISA kits. | through study completion, an average of 1 month | |
Other | Change in calprotectin across study periods | Changes to levels of calprotectin, a general inflammatory marker, assayed using ELISA kits. | through study completion, an average of 1 month | |
Other | Change in fasting glucose level across study periods | Changes to levels of fasting glucose assayed by a commercial lab. | through study completion, an average of 1 month | |
Primary | Change in gut microbiota composition across study periods | Assessment of whether statistically significant shifts in the community composition has occurred will be performed using PERMANOVA on the SILVA-annotated taxonomic output of 16S rRNA gene sequence data from stool taken on the last three days of each intervention. Visual presentation of beta-diversity will be presented using PCoA plots based on weighted and unweighted Unifrac distance measures. | through study completion, an average of 1 month | |
Secondary | Change in gut microbiota CAZyme abundance across study periods | Abundance of carbohydrate active enzymes (CAZymes) detected by shotgun sequencing of genomic DNA isolated from stool. Main comparison will be between high and low fiber diet intervention periods. | through study completion, an average of 1 month | |
Secondary | Change in gut microbiota mucolytic enzyme activity across study periods | Average bacterial sulfatase enzymatic activity of samples taken turing the last 3 days of each study period. Main comparison will be the average activity levels between high and low fiber diet intervention periods. | through study completion, an average of 1 month |
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