Fermented Foods for Rectal Cancer

Overseen by Doratha (Armen) Byrd, PhD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Inflammatory bowel conditions, Infectious disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the feasibility and acceptability of a dietary intervention (FEED-FF) that includes fermented foods (FF), among locally advanced rectal cancer patients and non-small cell lung cancer (NSCLC) patients, and to explore whether this diet can improve outcomes in rectal cancer patients receiving chemoradiation and NSCLC patients receiving immunotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop using probiotics if you are currently taking them.

What data supports the effectiveness of the treatment FEED-FF, High-Fermented Food Intervention, for rectal cancer?

Research suggests that fermented foods, like those rich in inulin, can produce short-chain fatty acids (SCFAs) such as butyrate, which have been shown to reduce tumor growth and induce cancer cell death in colon cancer models. Additionally, diets high in fiber, which is often found in fermented foods, are associated with a lower risk of colorectal cancer. ^{1 2 3 4 5}

Is the fermented food intervention safe for humans?

The research does not provide specific safety data for fermented foods in humans, but it suggests that dietary fibers and fermented foods can influence gut bacteria and produce beneficial compounds like short-chain fatty acids, which may have protective effects against colorectal cancer. ^{5 6 7 8 9}

How does the fermented food treatment for rectal cancer differ from other treatments?

The fermented food treatment for rectal cancer is unique because it uses fermented foods rich in dietary fiber and resistant starch, which produce short-chain fatty acids (SCFAs) like butyrate during fermentation. These SCFAs have protective effects against cancer by promoting apoptosis (programmed cell death) in cancer cells and reducing inflammation, offering a novel dietary approach compared to traditional drug therapies. ^{2 5 8 10 11}

Research Team

Doratha (Armen) Byrd, PhD, MPH

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for individuals with locally advanced rectal cancer who are about to receive chemoradiotherapy. Participants should be willing to follow a special diet that includes fermented foods and meet other study requirements.

Inclusion Criteria

Able to speak and read English

Able to consume foods orally

Able to provide informed consent

Exclusion Criteria

Already consuming ≥2 servings of fermented foods/day

Previously diagnosed with a mast cell disorder or histamine allergy

I have not taken antibiotics in the last month.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dietary Intervention

Participants receive a dietary intervention with fermented foods, consuming 3-6 servings per day from 1 week prior to treatment start through 12 weeks after treatment start.

13 weeks

3 visits (in-person) for biospecimen collection and surveys at baseline, week 6.5, and week 12.5

Treatment

Rectal cancer patients receive chemoradiation and NSCLC patients receive immunotherapy.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical response and quality of life assessments.

4 weeks

Treatment Details

Interventions

• FEED-FF (Behavioural Intervention)

Trial Overview The FEED Trial is testing the effects of a high-fermented food diet (FEED-FF) on patients with rectal cancer during their standard chemoradiotherapy treatment, aiming to see if it can improve outcomes.

Participant Groups

Group I: FEED-FF Experimental Treatment 1 Intervention

Participants will be asked to pick up the fermented foods at the Research Kitchen at Moffitt. Participants will be asked to eat 3-6 servings of FFs per day, from 1 week prior to treatment start through 12 weeks after treatment start/until the restaging scope is completed. At baseline, the end of week 6.5 and again at week 12.5, participants will be asked to provide biospecimens including a stool sample collected at home and a blood specimen collected in clinic. Participants will be asked to complete a food frequency questionnaire, a quality-of-life survey, two symptom related surveys, and a stool collection questionnaire at these same timepoints. After the dietary intervention, participants will be asked to complete an exit survey to provide feedback on the study and intervention.

Group II: Standard of Care (SUC) Active Control 1 Intervention

Participants will receive general healthy eating handouts similar to current usual care documents provided in clinic. These handouts will detail typical healthy foods and the suggested level of intake, or servings per day. At baseline, the end of week 6.5 and again at week 12.5, participants will be asked to provide biospecimens including a stool sample collected at home and a blood specimen collected in clinic. Participants will be asked to complete a food frequency questionnaire, a quality-of-life survey, two symptom related surveys, and a stool collection questionnaire at these same timepoints.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Patrick Hwu

H. Lee Moffitt Cancer Center and Research Institute

Chief Executive Officer since 2020

MD from The Medical College of Pennsylvania

Wade J. Sexton

H. Lee Moffitt Cancer Center and Research Institute

Chief Medical Officer

MD

Findings from Research

Patients with colorectal cancer consumed more energy from fats, proteins, and carbohydrates compared to matched control subjects, but their diets were significantly lower in cereal fiber, riboflavin, calcium, and phosphorus.

Higher intakes of cereal fiber, calcium, and total fiber were associated with a reduced risk of colorectal cancer, while high alcohol consumption was linked to an increased risk, supporting previous research on diet and cancer incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cereal fiber, calcium, and colorectal cancer. Arbman, G., Axelson, O., Ericsson-Begodzki, AB., et al.[2019]

The fermented nondigestible fraction (FNDF) from the Negro 8025 bean cultivar significantly inhibited the survival of human colon adenocarcinoma HT-29 cells, with a lethal concentration (LC50) of 13.63% FNDF, indicating its potential as a chemoprotective agent against colon cancer.

The FNDF produced higher levels of butyrate and had a lower pH compared to control, suggesting that the fermentation process enhances the production of beneficial short-chain fatty acids that may contribute to the observed anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermented nondigestible fraction from common bean (Phaseolus vulgaris L.) cultivar Negro 8025 modulates HT-29 cell behavior. Cruz-Bravo, RK., Guevara-Gonzalez, R., Ramos-Gomez, M., et al.[2017]

Fermentation supernatant fractions of inulin significantly increased short-chain fatty acids (SCFA) and decreased harmful bile acids, showing potential protective effects against colorectal cancer.

In human colon cell lines, particularly in early-stage cancer cells (LT97), the fermentation supernatant induced apoptosis and inhibited cell growth, suggesting that prebiotic fibers like inulin could play a role in cancer chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Munjal, U., Glei, M., Pool-Zobel, BL., et al.[2022]

In a study involving 216 male Fischer 344 rats, certain dietary fibers like polydextrose and wheat bran significantly reduced colon tumor incidence compared to a control diet, suggesting their protective effects against tumorigenesis.

The study found that the fermentation characteristics of different carbohydrates play a crucial role in tumor outcomes, with specific fibers leading to fewer tumors and lower tumor burden in the colon, highlighting the importance of dietary fiber type in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentable Carbohydrates Differentially Affect Colon Tumor Formation in Azoxymethane-Induced Male Fischer 344 Rats. Raju, J., Roberts, J., Chen, Q., et al.[2023]

Inulin-rich meat products, such as chorizo sausages and cooked ham, significantly reduced colon polyp formation by 49% in an animal model, indicating their potential as preventive foods against colorectal cancer.

The functional meat products not only increased beneficial short-chain fatty acids like propionate and butyrate but also altered gut microbiota composition, enhancing beneficial bacteria while reducing pro-inflammatory populations, suggesting a multifaceted approach to cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models. Fernández, J., Ledesma, E., Monte, J., et al.[2023]

Fermentation of wheat aleurone with probiotics LGG and Bb12 increased butyrate levels, which is beneficial for colon health, but only slightly enhanced fermentation efficiency.

The fermented aleurone significantly inhibited cell growth and promoted apoptosis in human colon adenoma and adenocarcinoma cells, suggesting its potential as a protective agent against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermented wheat aleurone enriched with probiotic strains LGG and Bb12 modulates markers of tumor progression in human colon cells. Borowicki, A., Michelmann, A., Stein, K., et al.[2017]

Dietary fiber plays a crucial role in reducing the risk of colonic cancer, primarily through the process of colonic fermentation, which produces beneficial short-chain fatty acids.

Resistant starch, which is not fully digested in the small intestine, serves as a significant source of fermentable substrate, potentially enhancing the protective effects against colon cancer by lowering colonic pH and reducing harmful secondary bile acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of carbohydrate fermentation in colon cancer prevention. Van Munster, IP., Nagengast, FM.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cereal fiber, calcium, and colorectal cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Fermented nondigestible fraction from common bean (Phaseolus vulgaris L.) cultivar Negro 8025 modulates HT-29 cell behavior. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Fermentable Carbohydrates Differentially Affect Colon Tumor Formation in Azoxymethane-Induced Male Fischer 344 Rats. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Pathogenicity of Fusobacterium nucleatum Modulated by Dietary Fibers-A Possible Missing Link between the Dietary Composition and the Risk of Colorectal Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Fermented wheat aleurone inhibits growth and induces apoptosis in human HT29 colon adenocarcinoma cells. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Mechanisms and experimental and epidemiological evidence relating dietary fibre (non-starch polysaccharides) and starch to protection against large bowel cancer. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Human gut flora-fermented nondigestible fraction from cooked bean ( Phaseolus vulgaris L.) modifies protein expression associated with apoptosis, cell cycle arrest, and proliferation in human adenocarcinoma colon cancer cells. [2012]

10. United States pubmed.ncbi.nlm.nih.gov

Fermented wheat aleurone enriched with probiotic strains LGG and Bb12 modulates markers of tumor progression in human colon cells. [2017]

11. England pubmed.ncbi.nlm.nih.gov

The role of carbohydrate fermentation in colon cancer prevention. [2019]