This study will evaluate if the Groningen Anti-Inflammatory Diet and the ileocolonic delivery of vitamin B2, B3 and C can positively influence the course of Crohn's disease and can positively alter the gut microbiome of Crohn's disease patients as well as healthy volunteers.

It is becoming increasingly more well known that diet and the microbiome have a pivotal role in the development and course of inflammatory bowel diseases (IBD). Strict exclusive enteral nutrition (EEN) can induce remission in Crohn's Disease (CD) and is the standard treatment in paediatric CD. Implementing a restrictive diet in adults is difficult; adult patients do not tend to adhere to EEN. Recently, the CD-exclusion diet (CDED) combined with partial enteral nutrition demonstrated to be effective in CD-patients with flares.

Additionally, accumulating evidence suggests that intake of vitamins can influence disease course, mainly by beneficially modulating the gut microbiota and gut redox potential, especially if the vitamins can be delivered to the colon.

Nevertheless, no dietary guidelines are available to physicians and patients. Due to complaints of certain foods and patients' eagerness to postpone new flares, patients start experimenting with their food. As patients with CD are already often malnourished, this poorly substantiated experimenting puts them even more at risk for malnutrition and could have a potential negative effect on their disease outcomes. Next, quality of life of patients decreases and healthcare costs will rise. Therefore, both patients and physicians are in desperate need of evidence for an anti-inflammatory dietary advice in CD. As compliance to a diet increases when they are supported by family members, their household members will also be asked to participate in the study. Simultaneously studying their healthy family members will also provide information of the effect of this anti-inflammatory diet or intake of lieocolonic-delivered vitamins on their microbiome and markers of inflammation and oxidative stress.

Inclusion Criteria CD patients:

• Participant understands the study procedures and signed an informed consent to participate in this study
• Previously diagnosed with CD; Montreal classification: L1 (Ileal), L2 (colonic), or L3 (ileocolonic).
• Low-mild disease activity (no clinically relevant symptoms and HBI<8 or CDAI <220)
• Evidence of mucosal inflammation (faecal calprotectin ≥100 μg/g)
• Able to attend to the outpatient clinic of the UMCG, Martini Hospital, MCL Leeuwarden or Isala
• ≥18 years of age
• Able to use oral feeding and willing to undergo a dietary intervention (Follow a diet or use a vitamin B2/B3/C supplement or placebo)

Inclusion Criteria healthy volunteers:

• Participant understands the study procedures and signed an informed consent to participate in this study
• Never been diagnosed with IBD or any other chronic inflammatory condition.
• Participant has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the investigator on the basis of medical history and routine laboratory test results.
• Able to attend to the outpatient clinic of the UMCG, Martini Hospital, MCL Leeuwarden or Isala
• ≥18 year of age
• Able to use oral feeding and willing to undergo a dietary intervention (Follow a diet or use a vitamin B2/B3/C supplement or placebo)

Exclusion Criteria CD patients:

• Life expectancy <12 months
• Active Crohn's disease (HBI≥8 or CDAI>220), or expecting drug intervention within 3 months
• Colonoscopy and colon cleansing in the past 3 months;
• Use antibiotics, probiotics (eg Yakult, Vifit, Activia) or specific prebiotics supplements 3 weeks prior to the start of the intervention
• Use of vitamin/mineral supplements 1 week prior to the start of the intervention (except for vitamin D and/or calcium)
• Use Methotrexate drugs or chronic use of antacids, H2 or proton-pump inhibitors
• With a history of GI disorders or GI surgery that are likely to interfere with the pH-dependent mode of action of the Colovit-capsule
• Patients with a pouch or stoma
• Pregnant or breastfeeding (or foreseen pregnancy during dietary intervention period)
• Swallowing disorders, not able to tolerate oral food, or use of tube feeding (EEN)
• Previously proven anaphylactic reaction to foods included in the food boxes
• Previously diagnosed with Celiac Disease or following a gluten-free diet
• Following a vegetarian or vegan diet

Exclusion Criteria healthy subjects:

• Life expectancy <12 months
• Previously diagnosed with IBD or any other chronic inflammatory condition
• Colonoscopy and colon cleansing in the past 3 months;
• Use antibiotics, probiotics (eg Yakult, Vifit, Activia) or specific prebiotics supplements 3 weeks prior to the start of the intervention
• Use of vitamin/mineral supplements 1 week prior to the start of the intervention (except for vitamin D and/or calcium)
• With a history of GI disorders or taken drugs that are likely to interfere with mode of action of interventions, such as chronic use of antacids or proton-pump inhibitors
• Abnormal clinical chemistry and haematology laboratory test results of clinical significance that in the judgment of the investigator would interfere with the participant's ability to comply with the study protocol (which might confound the interpretation of the study results), or put the participant at undue risk.
• Presence of a stoma
• History or presence of cancer in the prior two years, except for non-melanoma skin cancer.
• Recent history of (within 12 months of screening visit) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as >60g (men) / 40g (women) pure alcohol per day (1.5 l / 1 l beer resp. 0.75 l / 0.5 l wine).
• Pregnant or breastfeeding (or foreseen pregnancy during dietary intervention period) The method of contraception must be recorded in the source documentation.
• Swallowing disorders, not able to tolerate oral food, or use of tube feeding (EEN)
• Previously proven anaphylactic reaction to foods included in the food boxes
• Previously diagnosed with Celiac Disease or following a gluten-free diet
• Following a vegetarian or vegan diet

There is no plan to make individual participant data available to other researchers outside of the study team.