Dietary Fiber (Inulin) for Gut Health and Immune Response

Overseen By Yuriko Adkins, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: USDA, Western Human Nutrition Research Center

Must not be taking: NSAIDs, Antibiotics, Biologics, others

Disqualifiers: Cancer, HIV, Hypertension, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding inulin, a type of dietary fiber, to a low-fiber diet can boost good bacteria in the gut and improve immune response to vaccines. Researchers will compare inulin to maltodextrin, a placebo, to observe changes in gut health and immune function. The study seeks participants who consume less fiber than recommended and do not have certain health conditions, such as asthma requiring daily medication or recent surgeries. Participants will consume either inulin or maltodextrin and receive a vaccine to test these effects. As an Early Phase 1 trial, this research focuses on understanding how inulin works in people, offering participants a chance to contribute to groundbreaking scientific discovery.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including anti-inflammatory drugs, antibiotics, anti-hypertensive drugs, anti-malaria drugs, drugs affecting the immune system, and biologics. If you are on any of these medications, you may need to stop them to participate in the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that inulin is generally safe for most people. Studies have found that up to 20 grams of inulin per day is usually well-tolerated. In this trial, participants will take 12 grams per day, which falls within this safe range.

Experts indicate that inulin supplements are likely safe for short-term use. Many people use inulin to aid digestion and support the immune system, with most experiencing no serious side effects.

Overall, evidence suggests that inulin supplements are unlikely to cause harm for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using inulin for gut health and immune response because it is a dietary fiber with a unique ability to promote beneficial gut bacteria growth. Unlike traditional probiotics or antibiotics, inulin acts as a prebiotic, selectively feeding good bacteria and potentially enhancing the immune system's response to vaccines like Ty21a. This natural approach could offer a gentler and more sustainable way to boost gut health and immunity compared to conventional treatments.

What evidence suggests that inulin could be an effective treatment for gut health and immune response?

Studies have shown that inulin, which participants in this trial may receive, can increase the number of beneficial bacteria in the gut, such as Bifidobacterium. These bacteria play a crucial role in improving gut health and enhancing immune system function. Research indicates that inulin can also strengthen the gut and reduce inflammation, leading to less irritation. Some studies have found that inulin may aid in weight loss and improve insulin utilization, which is vital for managing blood sugar. Overall, these findings suggest that inulin could support gut health and boost the immune system. ^{4 6 7 8 9}

Who Is on the Research Team?

Danielle Lemay, PhD

Principal Investigator

USDA, ARS, Western Human Nutrition Research Center

Ryan Snodgrass, PhD

Principal Investigator

USDA, ARS, Western Human Nutrition Research Center

Mary Kable, PhD

Principal Investigator

USDA, ARS, Western Human Nutrition Research Center

Bess Caswell, PhD

Principal Investigator

USDA, ARS, Western Human Nutrition Research Center

Are You a Good Fit for This Trial?

This trial is for healthy men and women aged 18-50 with a BMI of 18.5-30.9 who don't eat enough fiber, defined as less than daily recommended amounts based on age and gender. Participants should not have used certain medications recently, including antibiotics or anti-malaria drugs, have no history of typhoid fever or GI surgery, are not pregnant or lactating, do not have chronic illnesses like diabetes or heart disease, and are willing to avoid some supplements during the study.

Inclusion Criteria

I am a male between 18 and 30 years old.

I am a woman aged 31-50 and drink less than 25g of alcohol daily.

I am a man aged 31-50 and consume less than 31 grams of alcohol daily.

Exclusion Criteria

I am taking medication for high blood pressure.

Regular blood or blood product donation and refusal to suspend donation

I have not had severe diarrhea or constant vomiting in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Vaccine Treatment

Participants consume 12 grams/day of inulin or maltodextrin for 3 weeks before the administration of the Ty21a vaccine

3 weeks

Vaccine Administration and Treatment

Participants continue consuming inulin or maltodextrin during the 1 week of vaccine administration

1 week

Post-Vaccine Treatment

Participants continue consuming inulin or maltodextrin for 1 week after the vaccine administration

1 week

Follow-up

Participants are monitored for changes in immune response, gut microbiome, and other health markers

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inulin
• Maltodextrin
• Ty21a Typhoid Fever Vaccine

Trial Overview The study tests if adding inulin (a type of dietary fiber) instead of maltodextrin (control) to participants' diets can improve gut health by increasing beneficial bacteria levels and enhancing immune response to the Ty21a typhoid vaccine. It will measure changes in gut microbes, inflammation reduction, vaccine response enhancement, and white blood cell adhesion molecule expression.

How Is the Trial Designed?

Group I: Inulin and Ty21a Vaccine Experimental Treatment 2 Interventions

Participants will consume 12 grams/day of inulin for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.

Group II: Maltodextrin and Ty21a Vaccine Placebo Group 2 Interventions

Participants will consume 12 grams/day of maltodextrin (control) for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.

Inulin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Inulin for:

• Dietary supplement
• Prebiotic

Approved in United States as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Canada as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Japan as Inulin for:

• Dietary supplement
• Prebiotic

Approved in China as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Switzerland as Inulin for:

• Dietary supplement
• Prebiotic

Who Is Running the Clinical Trial?

USDA, Western Human Nutrition Research Center

Lead Sponsor

Trials

64

Recruited

19,100+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Inulin fructans, derived from chicory root, are safe and well-tolerated dietary fibers that can be consumed up to 20 g per day, providing various health benefits.

They have direct effects on gut health, such as improving bowel function and promoting beneficial gut bacteria, as well as indirect effects on blood lipids and the immune system, suggesting potential for further research in energy balance and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of Inulin Fructans in the Human Diet. Schaafsma, G., Slavin, JL.[2021]

Inulin-type fructans, particularly oligofructose-enriched inulin, are effective prebiotics that enhance gut health by promoting the growth of beneficial bacteria and improving bowel habits, supported by numerous animal studies and human trials.

Inulin has been shown to reduce triglyceride levels in the blood and may help normalize blood lipids, with potential implications for reducing the risk of colon cancer, as ongoing human trials are investigating its effects in individuals at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing inulin-type fructans. Roberfroid, MB.[2021]

In a study involving 30 obese women over 3 months, treatment with inulin-type fructans (ITF prebiotics) significantly altered gut microbiota composition, increasing beneficial bacteria like Bifidobacterium and Faecalibacterium prausnitzii, which are linked to lower serum lipopolysaccharide levels.

The ITF prebiotics also resulted in a slight decrease in fat mass and changes in plasma metabolites, suggesting that these prebiotics can modestly influence host metabolism and may have implications for obesity and diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Dewulf, EM., Cani, PD., Claus, SP., et al.[2022]

In a 3-month randomized, placebo-controlled trial involving 24 obese patients, the intake of inulin-type fructans (ITF) significantly increased levels of beneficial gut bacteria, specifically Bifidobacterium, and reduced fecal calprotectin, a marker of gut inflammation.

The study suggests that ITF may help improve gut health in obese individuals by decreasing inflammation and potentially influencing gut microbiota-derived metabolites, although it did not significantly change short-chain fatty acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Neyrinck, AM., Rodriguez, J., Zhang, Z., et al.[2022]

Inulin-type fructans (ITF) have been shown to positively influence the intestinal microbiota by increasing beneficial bacteria such as Bifidobacterium and Lactobacillus, which can lead to improved gut health and function.

ITF intake is associated with several health benefits, including better intestinal barrier function, improved insulin sensitivity, lower triglycerides, enhanced mineral absorption, and increased feelings of fullness, although more research is needed to understand how chain length affects these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. Hughes, RL., Alvarado, DA., Swanson, KS., et al.[2023]

Inulin acts as a prebiotic that enhances the growth of beneficial Bifidobacterium bacteria and produces short-chain fatty acids (SCFAs) through fermentation, which can help prevent or treat metabolic disorders like obesity and type 2 diabetes.

While inulin has many health benefits, it can also cause gastrointestinal issues in some individuals, highlighting the need for careful dosage and further research on its long-term use and interactions with medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin fructans in diet: Role in gut homeostasis, immunity, health outcomes and potential therapeutics. Tawfick, MM., Xie, H., Zhao, C., et al.[2022]

Human studies indicate that inulin (IN) and oligofructose (OF) positively affect gut-associated immune functions, particularly in infants, by enhancing postnatal immune development and increasing fecal secretory IgA levels.

Animal studies reveal that IN/OF supplementation influences the intestinal immune system, particularly immune cells in Peyer's patches, through mechanisms like altering gut flora and increasing immunoregulatory metabolites, suggesting potential health benefits for infants and those with intestinal inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose: review of experimental data on immune modulation. Seifert, S., Watzl, B.[2023]

Inulin and oligofructose have a well-established bifidogenic effect, promoting beneficial bacteria in the gut across various age groups, which can enhance colonic function.

These prebiotics may help reduce harmful metabolites and promote immune responses, suggesting they could improve gut health and alleviate gastrointestinal discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Meyer, D., Stasse-Wolthuis, M.[2023]

In a study involving enterally fed elderly individuals, prebiotics in the diet led to an increase in beneficial gut bacteria, such as Bifidobacterium and Bacteroides, compared to a control group without prebiotics over a 10-week period.

The group receiving prebiotics maintained higher antibody titers against influenza vaccine strains (H1N1, H3N2) compared to the control group, suggesting that prebiotics may enhance the immunological response to vaccination in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced vaccination effect against influenza by prebiotics in elderly patients receiving enteral nutrition. Akatsu, H., Nagafuchi, S., Kurihara, R., et al.[2022]

In a study involving 40 healthy volunteers, long-chain inulin-type fructan (ITF) dietary fibers (DP10-60) significantly enhanced immune responses, leading to increased anti-HBsAg titers and specific immune cell activation after hepatitis B vaccination.

Shorter-chain ITFs (DP2-25) did not provide the same level of immune support, indicating that the chain length of dietary fibers is crucial for their effectiveness in boosting immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chain length-dependent effects of inulin-type fructan dietary fiber on human systemic immune responses against hepatitis-B. Vogt, LM., Elderman, ME., Borghuis, T., et al.[2023]

Both arabinoxylo-oligosaccharides (AXOS) and inulin significantly lowered the pH in gut fermentations, resulting in increased production of beneficial short-chain fatty acids like acetate, propionate, and butyrate, which are important for gut health.

The study found that AXOS and inulin differentially modulated gut microbiota composition and immune responses in a donor-specific manner, enhancing gut barrier function and immune markers such as IL-10 and IL-6.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on Microbial Metabolism and Composition, Which Immunomodulates Human Cells. Van den Abbeele, P., Taminiau, B., Pinheiro, I., et al.[2018]

Fermentation of various dietary fibers, particularly oat β-glucan, significantly enhances gut barrier integrity and mucus production, suggesting these fibers can improve gut health.

In models of compromised gut barriers, oat β-glucan and maltodextrin fermentation products were particularly effective in restoring gut integrity, highlighting their potential as therapeutic agents for gut-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro. Pham, VT., Seifert, N., Richard, N., et al.[2020]

Citations

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Differential effects of inulin and fructooligosaccharides on ... Notably, in this study, although FOS did not improve glycemic metabolism, it reduced HCY level, indicating a potential cardiovascular benefit.

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The Prebiotic Potential of Inulin-Type Fructans Beneficial health effects reported following ITF intake include improved intestinal barrier function, improved laxation, increased insulin sensitivity, ...

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Prebiotic effect of oligofructose after 2 weeks ... This study is the first to demonstrate a significant increase in bifidobacteria coinciding with increased stool frequency after a very low dose of 2.5 g/d ...

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Link between gut microbiota and health outcomes in inulin ... Conclusions. Inulin-enriched diet is able to promote weight loss in obese patients, the treatment efficiency being related to gut microbiota characteristics.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1224092/full

Immunomodulatory effects of inulin and its intestinal ... Results in animal IBD models and humans suggest that inulin intake can help to improve the intestinal mucosal barrier and suppress intestinal inflammation (149 ...

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Immunomodulatory effects of inulin and its intestinal ... Recently, several studies have found that dietary supplementation of inulin can improve metabolic function and regulate intestinal immunity.

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1048/inulin

Inulin - Uses, Side Effects, and More When taken by mouth: Inulin is likely safe for most people in the amounts found in foods. It is possibly safe in adults when taken as a supplement, short-term.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0273230099913491

Evaluation of Safety of Inulin and Oligofructose as Dietary ... A series of clinical studies has been reported which shows that up to 20 g/day of inulin and/or oligofructose is well tolerated.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2475299122143787

Health Effects and Sources of Prebiotic Dietary Fiber Prebiotic dietary fibers act as carbon sources for primary and secondary fermentation pathways in the colon, and support digestive health in many ways.