Influence of Low FODMAP and

Gluten-Free Diets on Disease Activity

and Intestinal Microbiota in Patients
with Non-Celiac Gluten Sensitivity
Walburga Dieterich, Detlef Schuppan, Monic Schink, Raphaela Schwappacher,
Stefan Wirtz, Abbas Agaimy, Markus F. Neurath, Yurdagül Zopf

By: Julia Wang

Review
Celiac Disease vs. Non-Celiac Gluten Sensitivity
• CD: autoimmune genetic disorder with immune inflammation of SI in
exposure to gluten peptides
• Affects 1% of worldwide population
• Diagnosed by blood markers
• NCGS: activation of intestinal innate immunity in the absence of CD
and wheat allergy
• Reaction to gluten-containing products
• Intestinal and extra-intestinal symptoms
• No villi atrophy or serological markers
Review
What is low FODMAP?
• Acronym for Fermentable Oligo- Di- Monosaccharides And Polyols
• Short-chain carbohydrates poorly digested and absorbed
• Symptoms: cramping, diarrhea, constipation, bloating, flatulence
• 6 groups:
• Fructose: apple, mango, honey
• Lactose: milk, cheese, dairies
• Sorbitol: apricot, plum, prune
• Mannitol: mushroom, cauliflower, celery
• Fructan: asparagus, broccoli, cabbage
• Galactan (GOS): lentils, kidney beans
Review
Gluten-Containing Cereals:
• High ATI (amylase-trypsin-inhibitors)
• Resistant to food processing and digestion
• Activate gut myeloid cells – trigger intestinal inflammation

Gluten-Free Diet:
• Wheat, barley, rye
• vs. FODMAP:
• Restrict gluten protein rather than CHO
• Gluten products may be consumed if priorly fermented in low FODMAP
• Australia: rolled oats are not GF but gluten-friendly
Study
• Purpose: To analyze the effects of low FODMAP and GFD on GI, mucosal
inflammation, and psychological wellbeing on NCGS and control group
• Study Design: clinical trial
• Study Method:
• 19 NGCS
• None with autoimmune disease, wheat allergy, 1st degree relatives with CD
• All had intestinal symptoms
• 10 healthy individuals (CG)
Study Design
• Prior study: Western Diet, minimal 2 meals with gluten (10g) daily, 4w
before start of study
• Low FODMAP diet, 2 weeks
• Transition period, 5 days
• GFD, 2 weeks
• Collection of stool samples after end of low FODMAP and end of GFD
• Questionnaires about GI symptoms and psychological well being, before
and after end of each diet
Study Design

• Daily record of stool consistency (Bristol stool chart)

• Nutritional analysis of Ptns, Fats and CHO, with ≠ data for lactose,
fructose, sorbitol, mannitol, and xylitol

• Primary Outcome: recovery from GI symptoms in NCGS

• Secondary Outcome: improvement of psychological symptoms,
normalization of Goblet cells, dietary effect on microbiota in NCGS
Study Results
• Diet Impact:
• Low FODMAP: reduced daily calorie intake and significant reduction in lactose,
fructose, maltose and sorbitol
• GFD: fewer calories in NCGS group
• GI Symptoms:
• Low FODMAP showed significant improvements in Gastrointestinal Symptom
Rating Scale (GSRS), (p=.001)
• GFD showed further improvements (p <.05)
• Higher significant improvements in abdominal pain, diarrhea and constipation
under GFD than low FODMAP
• Lose stool at beginning of study was normalized under the GFD in NCGS
Study Results
Study Results
• Psychological Well Being:
• NCGS: compromised well being was significantly improved with low FODMAP, and
further improved under GFD – final value comparable to CG
• Control: reduced well being under low FODMAP – dietary restrictions

• Goblet Cells:
• Mucosa inflammation significantly decreased in all but one NCGS after GFD
• Significant decrease of Goblet cells on GFD
Study Results
Microbiota:
• Pre-study:
• Abundant Bacteroidetes in both groups, higher value in CG
• Lower Firmicutes in CG than NCGS
• WD: increased Firmicutes and reduced Bacteroidetes in NCGS compared to CG
• Low FODMAP: diminished Actinobacteria and enriched Firmicutes (dropped in GFD)
• GFD: significant increase in Bacteroidetes and drop in Firmicutes than low FODMAP
Discussion
NCGS showed:
• Significant improvement in GI symptoms under low FODMAP diet
• Recent study shows more severe GI symptoms with fructans than gluten
• Suggest other wheat components as cause of pathogenesis in NCGS
• No mucosal damage, and IEL increase in only 42%
• Intraepithelial lymphocyte is a sign of intestinal immune activation
• Improved GI and psychological symptoms after low FODMAP
Conclusion
• Persistent differences in microbiota suggest clinical symptoms may be
caused by factors other than microorganisms
• Increased Firmicutes and decreased Bacteroides
• Improved GI symptoms but persistent trends of specific populations
• Decreased Bifidobacteriaceae (Actinobacteria) in low FODMAP and GFD
• Valuable probiotic for GI disorders
• Greater metabolomics variability suggest that NCGS microbiota may be
more susceptible to nutrient changes
• Studies show more microbiota composition variation in IBS than healthy individuals
Conclusion

• GFD decreased number of Goblet cells in NCGS

• Goblet cells: main mucin producers for mechanical barrier and
sequestration of antibacterial peptides in SI

• Increased mucus production in NCGS under gluten-containing diet

suggests adaptation to microbial dysbalance/nutrient stimulation
Strength & Limitations
Strength:
• Detailed nutritional consultation prior study and supervision by RD
• High dietary compliance from participants

Limits:
• Open design (no blinding)
• Short intervention period (2 weeks)