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

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to determine if adding dietary fiber, such as inulin, to a diet that does not have enough fiber would raise the levels of potentially beneficial bacteria, such as Bifidobacterium, in the gut. There is evidence to suggest that these microbes can affect gut health and immune response, including to vaccines. The investigators will examine how inulin in the diet (compared to the maltodextrin control) (1) causes changes in the composition and function of the gut microbes, (2) reduces gut inflammation and gut leakiness caused by the vaccine, (3) increases immune response to vaccination, and (4) changes the expression of important adhesion molecules on the surface of white blood cells. Intestinal and whole-body responses will be measured in all participants.

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 inulin safe for human consumption?

Inulin is generally considered safe and well-tolerated in humans up to 20 grams per day, although some people may experience mild gastrointestinal symptoms. It is a type of dietary fiber found in many foods and is used to improve gut health and immune response. ^{1 2 3 4 5}

How is the treatment Inulin different from other treatments for gut health and immune response?

Inulin is unique because it is a prebiotic fiber that specifically promotes the growth of beneficial gut bacteria, which can improve gut health and immune function. Unlike other treatments, it is not digested by the body but is fermented in the colon, leading to beneficial changes in gut microbiota and systemic health effects. ^{2 4 6 7 8}

What data supports the effectiveness of the treatment Inulin, Fructo-oligosaccharides, Prebiotic fiber, Maltodextrin, and Ty21a Typhoid Fever Vaccine for gut health and immune response?

Research shows that inulin and fructo-oligosaccharides, as prebiotic fibers, can improve gut health by enhancing beneficial gut bacteria and reducing inflammation. Additionally, these fibers may boost immune function by positively affecting gut-associated immune tissues, which could be beneficial for overall health. ^{4 9 10 11 12}

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

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]

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]

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]

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]

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]

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 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]

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]

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]

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-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]

Citations

1. Germany 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. [2022]

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

Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on Microbial Metabolism and Composition, Which Immunomodulates Human Cells. [2018]

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

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro. [2020]

4. Japan pubmed.ncbi.nlm.nih.gov

Enhanced vaccination effect against influenza by prebiotics in elderly patients receiving enteral nutrition. [2022]

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

Inulin and oligofructose: review of experimental data on immune modulation. [2023]

6. England 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. [2022]

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

Significance of Inulin Fructans in the Human Diet. [2021]

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

The bifidogenic effect of inulin and oligofructose and its consequences for gut health. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Inulin fructans in diet: Role in gut homeostasis, immunity, health outcomes and potential therapeutics. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Chain length-dependent effects of inulin-type fructan dietary fiber on human systemic immune responses against hepatitis-B. [2023]

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

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Introducing inulin-type fructans. [2021]