Ignite Creation Date:
2024-05-06 @ 2:33 PM
Last Modification Date:
2024-10-26 @ 1:33 PM
Study NCT ID:
NCT04352231
Status:
COMPLETED
Last Update Posted:
2022-12-08
First Post:
2020-02-26
Brief Title:
Luxembourgish Fiber Cohort
Sponsor:
Luxembourg Institute of Health
Organization:
Luxembourg Institute of Health
Study Overview
Official Title:
From Mouse to Man Translating Findings in Mouse Study Into a Human Cohort Luxembourgish Fiber Cohort Lux-FiCo
Status:
COMPLETED
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Lux-FiCo
Brief Summary:
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 eg 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 guts 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
Detailed Description:
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 gday 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
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 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 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 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 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 gd more than the low-fiber diet In addition to dietary records the investigators will administer questionnaires obtain basic clinical measures blood pressure weight height waistthigh 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 n15 in each sequence group a total sample size of N30 to have 875 power to detect a -05 difference in means for alpha diversity Shannon index under the two diet conditions 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 in conjunction with the LIH study team and delivered by Paul Eischen Traiteur a partner catering service 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 a Participant Diary to log their diet throughout the study in the form of daily 24 hour food recalls 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 has been granted ethical approval by the Luxembourg Ministry of Health Ref 835x38895 and by Comité National dEthique de Recherche CNER Ref 20191103
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 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 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 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 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 gd more than the low-fiber diet In addition to dietary records the investigators will administer questionnaires obtain basic clinical measures blood pressure weight height waistthigh 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 n15 in each sequence group a total sample size of N30 to have 875 power to detect a -05 difference in means for alpha diversity Shannon index under the two diet conditions 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 in conjunction with the LIH study team and delivered by Paul Eischen Traiteur a partner catering service 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 a Participant Diary to log their diet throughout the study in the form of daily 24 hour food recalls 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 has been granted ethical approval by the Luxembourg Ministry of Health Ref 835x38895 and by Comité National dEthique de Recherche CNER Ref 20191103
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None