Exploring Mechanism of Action of Dietary Fibre on the Gut Microbiota and Metabolites

NCT05906589 | Completed

• 1 other identifier: 501
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Cancer patients receiving pelvic radiotherapy suffer side effects to the intestine, including diarrhoea and occasionally rectal bleeding, often worsened by chemoradiation. Many pelvic radiotherapy patients receive a form of dietary fibre, psyllium husk, to manage their diarrhoeal symptoms. There is evidence in mice that dietary fibre supplementation can improve tumour response and reduce normal tissue side effects caused by radiation. If this were to be confirmed in humans, it would be a major advance in patient treatment. The investigators will conduct a study in healthy subjects to assess mechanisms and response to dietary fibre. The investigators will conduct a within-subject diet intervention study on healthy older adults (\>60 years old) to determine if a subset of the population are responders to dietary fibre manipulation, using inulin with or without psyllium. This will allow assessment of the physiological impact of dietary fibre. Participants will receive placebo, inulin, or psyllium plus inulin in random order (6 possible combinations) for two weeks each with two-week washout periods. Baseline faecal microbial activity, short chain fatty acid (SCFA) concentrations, and habitual fibre intake, determined by dietary questionnaires/food diaries will be used to identify individuals in whom dietary fibre manipulation might have a positive impact. Individuals who respond to dietary fibre supplementation may be found to have elevated levels of some SCFAs and significantly increased relative abundance of certain microbiota. Dietary parameters, bacterial relative abundance and SCFA levels will be correlated with plasma cytokine levels.

Conditions

Psyllium; Inulin

Keywords

Dietary fibre; Dietary fiber; Gut microbiota

Outcome Measures

Primary Outcomes (2)

• Microbial composition using 16S sequencing

  To explore the effect of inulin and psyllium plus inulin on microbial composition at baseline and after a 14-day intervention.

  11 weeks per participant

• Short Chain Fatty Acid (SCFA) levels

  To explore the effect of inulin and psyllium plus inulin on short chain fatty acid levels at baseline and after a 14-day intervention.

  11 weeks per participant

Secondary Outcomes (9)

• Tolerability of Inulin defined by questionnaire 'quality of life' and 'gastrointestinal wellbeing'

  11 weeks per participant

• Tolerability of psyllium defined by questionnaire 'quality of life SF36' and 'gastrointestinal wellbeing'

  11 weeks per participant

• Rate of habitual fibre intake before and during the intervention

  11 weeks per participant

• Faecal SCFA concentrations

  11 weeks per participant

• Elevated plasma SCFAs

  11 weeks per participant

Study Arms (3)

Inulin

EXPERIMENTAL

The participant will be asked to administer the provided doses of 8g inulin twice daily.

Dietary Supplement: Inulin

Inulin + psyllium

EXPERIMENTAL

The participant will be asked to administer the provided doses of 8g inulin + 3.5g psyllium twice daily.

Dietary Supplement: Inulin; Dietary Supplement: Psyllium

Maltodextrin

PLACEBO COMPARATOR

The participant will be asked to administer the provided doses of 8g maltodextrin twice daily.

Dietary Supplement: Maltodextrin

Interventions

Inulin DIETARY_SUPPLEMENT

The participant will take inulin twice daily over a 14 day period.

Inulin; Inulin + psyllium

Psyllium DIETARY_SUPPLEMENT

The participant will take psyllium twice daily over a 14 day period.

Also known as: Ispaghula husk

Inulin + psyllium

Maltodextrin DIETARY_SUPPLEMENT

The participant will take maltodextrin twice daily over a 14 day period.

Maltodextrin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>60 years old

You may not qualify if:

• Oral antibiotic use (within the past 3 months due to impact on gut microbiota).
• Anti-coagulants (Warfarin).
• Carbamazepine (epilepsy)
• Digoxin (heart conditions)
• Mesalazine (gut problems)
• Regular use of anti-constipation medication/laxatives.
• Food allergies, self-reported food sensitivity or intolerance.
• Type 1 or Type 2 diabetes.
• Coeliac disease or gluten intolerance.
• Metformin intake.
• Bowel obstruction
• Muscle weakness of the bowel
• Phenylketonuria.
• Anyone with unsuitable veins for blood sampling.
• Anyone with chronic constipation (\>3 days without defaecation).

Sponsors & Collaborators

• University of Aberdeen: lead

Study Sites (1)

Rowett Institute

Aberdeen, AB25 2ZD, United Kingdom

Location

Related Publications (14)

• Wang L, Wang X, Zhang G, Ma Y, Zhang Q, Li Z, Ran J, Hou X, Geng Y, Yang Z, Feng S, Li C, Zhao X. The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review. Radiat Oncol. 2021 Sep 25;16(1):187. doi: 10.1186/s13014-021-01899-y.

  PMID: 34563216 BACKGROUND

• Bishehsari F, Engen PA, Preite NZ, Tuncil YE, Naqib A, Shaikh M, Rossi M, Wilber S, Green SJ, Hamaker BR, Khazaie K, Voigt RM, Forsyth CB, Keshavarzian A. Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA Production, and Suppresses Colon Carcinogenesis. Genes (Basel). 2018 Feb 16;9(2):102. doi: 10.3390/genes9020102.

  PMID: 29462896 BACKGROUND

• Carretta MD, Quiroga J, Lopez R, Hidalgo MA, Burgos RA. Participation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer. Front Physiol. 2021 Apr 8;12:662739. doi: 10.3389/fphys.2021.662739. eCollection 2021.

  PMID: 33897470 BACKGROUND

• Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119. doi: 10.1016/B978-0-12-800100-4.00003-9.

  PMID: 24388214 BACKGROUND

• Kaczmarczyk MM, Miller MJ, Freund GG. The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer. Metabolism. 2012 Aug;61(8):1058-66. doi: 10.1016/j.metabol.2012.01.017. Epub 2012 Mar 7.

  PMID: 22401879 BACKGROUND

• Olopade FA, Norman A, Blake P, Dearnaley DP, Harrington KJ, Khoo V, Tait D, Hackett C, Andreyev HJ. A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy. Br J Cancer. 2005 May 9;92(9):1663-70. doi: 10.1038/sj.bjc.6602552.

  PMID: 15856043 RESULT

• Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell. 2018 Apr 9;33(4):570-580. doi: 10.1016/j.ccell.2018.03.015.

  PMID: 29634945 RESULT

• Reis Ferreira M, Andreyev HJN, Mohammed K, Truelove L, Gowan SM, Li J, Gulliford SL, Marchesi JR, Dearnaley DP. Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy. Clin Cancer Res. 2019 Nov 1;25(21):6487-6500. doi: 10.1158/1078-0432.CCR-19-0960. Epub 2019 Jul 25.

  PMID: 31345839 RESULT

• Ogata M, Ogita T, Tari H, Arakawa T, Suzuki T. Supplemental psyllium fibre regulates the intestinal barrier and inflammation in normal and colitic mice. Br J Nutr. 2017 Nov;118(9):661-672. doi: 10.1017/S0007114517002586.

  PMID: 29185927 RESULT

• Llewellyn SR, Britton GJ, Contijoch EJ, Vennaro OH, Mortha A, Colombel JF, Grinspan A, Clemente JC, Merad M, Faith JJ. Interactions Between Diet and the Intestinal Microbiota Alter Intestinal Permeability and Colitis Severity in Mice. Gastroenterology. 2018 Mar;154(4):1037-1046.e2. doi: 10.1053/j.gastro.2017.11.030. Epub 2017 Nov 23.

  PMID: 29174952 RESULT

• Ramirez-Farias C, Slezak K, Fuller Z, Duncan A, Holtrop G, Louis P. Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br J Nutr. 2009 Feb;101(4):541-50. doi: 10.1017/S0007114508019880. Epub 2008 Jul 1.

  PMID: 18590586 RESULT

• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5.

  PMID: 26541606 RESULT

• Then CK, Paillas S, Wang X, Hampson A, Kiltie AE. Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation. BMC Biol. 2020 Aug 19;18(1):102. doi: 10.1186/s12915-020-00836-x.

  PMID: 32811478 RESULT

• Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, Brown D, Stares MD, Scott P, Bergerat A, Louis P, McIntosh F, Johnstone AM, Lobley GE, Parkhill J, Flint HJ. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011 Feb;5(2):220-30. doi: 10.1038/ismej.2010.118. Epub 2010 Aug 5.

  PMID: 20686513 RESULT

MeSH Terms

Interventions

Inulin; Psyllium; ispaghula seed; maltodextrin

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures

Study Officials

• Anne E Kiltie, Prof

  University of Aberdeen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study will be double blind, meaning both the investigator and the participants will not know if the participants are receiving inulin, psyllium plus inulin or the placebo. However, there is some difference in the consistency of the powders. The supplements will be labelled A, B and C by an independent party otherwise not involved in the study, and the investigator and participants will not know which supplement is which letter during the study period.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The participants will be randomly allocated to one of the 6 different intervention combinations for the supplements ((A) placebo; (B) inulin; (C) psyllium plus inulin) with the same number of participants in each of the combinations. There are 6 possible combinations: * A \> B \> C * B \> A \> C * C \> B \> A * A \> C \> B * C \> A \> B * B \> C \> A

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: June 18, 2023
• Study Start: September 7, 2023
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)