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Clinical Trial
. 2018 Dec 19;18(1):338.
doi: 10.1186/s12906-018-2403-6.

Dietary geraniol ameliorates intestinal dysbiosis and relieves symptoms in irritable bowel syndrome patients: a pilot study

Fernando Rizzello  1 , Chiara Ricci  2 , Michela Scandella  1 , Elena Cavazza  1 , Elisabetta Giovanardi  1 , Maria Chiara Valerii  1   3 , Massimo Campieri  1 , Antonietta Comparone  3 , Luigia De Fazio  3 , Marco Candela  4 , Silvia Turroni  4 , Enzo Spisni  5
Affiliations
Clinical Trial

Dietary geraniol ameliorates intestinal dysbiosis and relieves symptoms in irritable bowel syndrome patients: a pilot study

Fernando Rizzello et al. BMC Complement Altern Med. .

Abstract

Background: (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency.

Methods: Ge-OH was orally administered at a maximum daily dose of 8 mg kg(- 1) body weight for four weeks in a delayed release formulation capable of reaching the colon. Fecal microbiota and blood cytokines were analyzed before and after Ge-OH treatment, as well as IBS symptomatology by using Visual Analogue Scale (VAS-IBS).

Results: The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1β, a chemokine found to be increased in several IBS patients.

Conclusion: Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients.

Trial registration: ISRCTN47041881 , retrospectively registered on 19th July 2018.

Keywords: Dysbiosis; Geraniol; Inflammation; Irritable bowel syndrome (IBS); Microbiota.

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Conflict of interest statement

Ethics approval and consent to participate

Patients were informed of the full nature and purpose of the study, and provided written informed consent before entering the trial. The study was conducted in conformity with the principles of Declaration of Helsinki and Good Clinical Practice. The study was approved by the Ethics Committee of the AOU Policlinico S. Orsola-Malpighi; CE code 100/2013/U/Sper and by the Ethics Committee of the ASST Spedali Civili di Brescia; CE code NP2047.

Consent for publication

All patients gave explicit written consent for data publication in aggregated form.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of study protocol
Fig. 2
Fig. 2
Total score of the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) questionnaire administered at T1, T2 and T3. Data for the whole IBS cohort and for IBS subtypes are expressed as mean ± SD. *P < 0.05 if compared to T1; ** P < 0.01 if compared to T1 (Student’s T test)
Fig. 3
Fig. 3
Plasma cytokine variations measured at T1, T2 and T3. Cytokines were determined using a 13-plex mouse bead immunoassay kit. Levels of IL-2 (a), IL-4 (b), IL-8 (c), IL-12 (d), IL-17A (e), IFN-γ (f), MIP-1β (g) and MCP-1 (h) are shown for the whole IBS cohort and for IBS subtypes. Data are expressed as mean ± SD of at least three replicates. Calculated P values were corrected for multiple comparisons by using the Benjamini-Hochberg method. *P < 0.05 if compared to T1
Fig. 4
Fig. 4
Gut microbiota signatures in IBS. a Box plots showing the distribution of Simpson diversity values in IBS patients (IBS-A, red; IBS-D, orange; IBS-C, black) and healthy controls (HC, green). A significant difference between IBS patients and HC was found (Wilcoxon test, P = 9 × 10− 6). b Principal component analysis of Euclidean distances between the genus-level intestinal microbial profiles (same color code as in A). Ellipses include 99% confidence area based on the standard error of the weighted average of sample coordinates. A significant separation between IBS and HC samples was found (permutation test with pseudo-F ratios, P = 2 × 10− 5). c Genus-level microbial signatures of IBS, shown as Log2-fold changes between IBS and control samples. Orange, taxa more abundant in IBS; green, taxa more abundant in HC. Wilcoxon test, P < 0.05
Fig. 5
Fig. 5
Impact of geraniol-based intervention on the intestinal microbiota structure in IBS patients. a Principal component analysis of Euclidean distances between the genus-level intestinal microbial profiles of IBS patients at the baseline (orange), after four-week intervention (red), and at follow-up after a further four weeks (olive green). Ellipses include the 99% confidence area based on the standard error of the weighted average of sample coordinates. A trend towards decreasing PC2 values after the intervention was observed (Wilcoxon test, P = 0.14). b Box plots showing the distribution of the relative abundance values of IBS discriminant taxa over time (T1, baseline; T2, after four-week intervention; T3, at follow-up). Data are shown for the whole IBS cohort and for IBS subtypes. The increase in the relative abundance of Collinsella and Faecalibacterium at T2 compared to the baseline (T1) was statistically significant (*, Wilcoxon test, P = 0.04)
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