Humanized Prebiotics for Gut Health

Overseen By Sylvia Becker-Dreps, MD, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Age, Pregnancy, Breastfeeding

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

63 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that Humanized Prebiotics for Gut Health is an effective treatment?

The available research shows that Humanized Prebiotics for Gut Health, also known as Galacto-oligosaccharides (GOS), are effective in promoting gut health. Studies indicate that GOS help in the growth of beneficial bacteria like bifidobacteria and lactobacilli, which are important for a healthy gut. They also improve gut barrier function and inhibit harmful bacteria from sticking to the gut lining. In particular, GOS have been shown to be beneficial in conditions like ulcerative colitis and during infections, as they help protect the gut lining. Additionally, GOS have been found to alleviate stress in the gut of young animals, suggesting their protective role. Overall, GOS are recognized for their positive impact on gut health compared to other similar treatments. ^{1 2 3 4 5}

What safety data is available for Humanized Prebiotics (GOS)?

The safety data for Galacto-oligosaccharides (GOS) includes its use as a prebiotic that is generally recognized for its health benefits, such as promoting beneficial gut bacteria and regulating gut microbiota. However, there have been reports of allergies related to GOS, particularly in atopic children in the South East Asian region. Overall, GOS is considered safe for most individuals, but potential allergic reactions should be noted. ^{1 2 3 5 6}

Is the treatment Galacto-oligosaccharides (GOS) promising for gut health?

Yes, Galacto-oligosaccharides (GOS) are promising for gut health. They help grow good bacteria in the gut, similar to what is found in human milk, and can improve gut health by balancing the bacteria in the intestines. This can lead to better digestion and a stronger immune system. ^{1 2 3 7 8}

What is the purpose of this trial?

This study aims to establish the safety of a 15 g/day dose of pure prebiotics ß(1-4) galacto-oligosaccharides (GOS) and GOS enriched with N-Acetyl-D-lactosamine, a building block of gut glycoproteins and human milk oligosaccharides (LAcNac, humanized GOS, hGOS) in healthy adult individuals. The safety and tolerability of the dose and the biological signature of GOS and hGOS in healthy adults will be established through a pilot clinical trial to assess GOS and hGOS effects vs placebo on (i) gastrointestinal adverse effects as measured by the Gastrointestinal Symptom and Severity Checklist (GSSC), (ii) increased abundance of beneficial gut bacteria and restoration of the gut microbiome saccharolytic potential, (iii) modulation of biomarkers of inflammation and (iv) evaluation of intestinal barrier function.

Research Team

Sylvia Becker-Dreps, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

Healthy adults aged 18-55, non-smokers with a BMI of 18.5-32, can join this trial. They must be able to consent, consume prebiotics or placebo for 4 weeks, keep a food diary, and provide stool and blood samples. It's open to all races, ethnicities, genders in North Carolina.

Inclusion Criteria

Individuals must be able to give informed consent.

My race, ethnicity, or gender does not affect my eligibility.

Subjects willing and able to record daily food consumption using the CDC My Food Diary questionnaire.

Exclusion Criteria

I am under 18 or over 55 years old.

Pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10-15 g/day of GOS or hGOS or placebo for 4 weeks to assess changes in gut microbiome and other health markers

4 weeks

2 visits (in-person) for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Galacto-oligosaccharides (GOS)
• Humanized Galacto-oligosaccharides (hGOS)
• Matching Placebo

Trial Overview The study tests the safety of two types of prebiotics: regular GOS and 'humanized' GOS (hGOS), against a placebo. It looks at their effects on gut health by checking for digestive side effects, beneficial bacteria growth in the gut microbiome, inflammation markers and intestinal barrier function.

Participant Groups

Group I: lactosamine-enriched "humanized" galacto-oligosaccharides (hGOS) Experimental Treatment 1 Intervention

The treatment will consist of 10-15 g/day of hGOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks since the research team has shown in adult individuals that a 4-wk period allows for the observation of changes to the gut microbiome. The study will end after the second time-point sample collection at 4 weeks.

Group II: galacto-oligosaccharides (GOS) Experimental Treatment 1 Intervention

The treatment will consist of 10-15 g/day of GOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks since the research team has shown in adult individuals that a 4-wk period allows for the observation of changes to the gut microbiome. The study will end after the second time-point sample collection at 4 weeks.

Group III: Placebo Placebo Group 1 Intervention

The placebo comparator treatment will consist of 10-15 g/day placebo powder, that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks to mirror the treatment arms. The study will end after the second time-point sample collection at 4 weeks.

Galacto-oligosaccharides (GOS) is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Galacto-oligosaccharides for:

• Food additive
• Prebiotic supplement

Approved in United States as Galacto-oligosaccharides for:

• Generally Recognized as Safe (GRAS) for use in foods
• Prebiotic supplement

Approved in Canada as Galacto-oligosaccharides for:

• Approved for use in infant formula and other foods
• Prebiotic supplement

Approved in Japan as Galacto-oligosaccharides for:

• Approved for use in foods for specified health uses (FOSHU)
• Prebiotic supplement

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

North Carolina Translational and Clinical Sciences Institute

Collaborator

Trials

61

Recruited

4,600+

Findings from Research

In a study involving BALB/c mice, 4 weeks of galacto-oligosaccharides (GOS) ingestion increased sucrase activity in the small intestine, suggesting a potential enhancement of carbohydrate digestion.

GOS ingestion also doubled the total protein content in the intestinal mucosa and increased mucin content, indicating a positive effect on gut health without altering villus height or inflammatory markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of galacto-oligosaccharide ingestion on the mucosa-associated mucins and sucrase activity in the small intestine of mice. Leforestier, G., Blais, A., Blachier, F., et al.[2022]

Galacto-oligosaccharides (GOS) are beneficial indigestible components that can improve gut health by fermenting in the colon to produce short-chain fatty acids, which help regulate intestinal flora.

GOS has shown effectiveness in enhancing gut microbiota balance and boosting immunity, and it may have specific positive effects on conditions like ulcerative colitis, making it a valuable prebiotic for human health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological activity of galacto-oligosaccharides: A review. Mei, Z., Yuan, J., Li, D.[2022]

Galactooligosaccharides (GOS) significantly increased the growth of beneficial Lactobacillus strains in both piglets and mice, which helped alleviate Salmonella infections, indicating their potential as a prebiotic for gut health.

Different Lactobacillus strains showed unique protective mechanisms: L. delbrueckii reduced intestinal inflammation by inhibiting specific signaling pathways, while L. johnsonii prevented Salmonella from adhering to gut cells, highlighting the varied roles of GOS-enriched probiotics in intestinal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strain specificity of lactobacilli with promoted colonization by galactooligosaccharides administration in protecting intestinal barriers during Salmonella infection. Wu, Y., Zhang, X., Liu, X., et al.[2023]

Galacto-oligosaccharides (GOS) promote the growth of beneficial gut bacteria, such as bifidobacteria and lactobacilli, and improve gut barrier function, making them valuable as prebiotics, especially in infant formulations.

GOS are produced through a controlled reaction involving lactose transgalactosylation, but there are still technological challenges in scaling up this production process for industrial use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galacto-oligosaccharides as infant prebiotics: production, application, bioactive activities and future perspectives. Ambrogi, V., Bottacini, F., Cao, L., et al.[2023]

In a study involving 18 neonatal piglets, early-life supplementation with galacto-oligosaccharides (GOS) significantly reduced oxidative stress caused by lipopolysaccharide (LPS) exposure, as evidenced by lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA).

GOS supplementation not only improved gut function by enhancing antioxidant and digestive enzyme activities but also activated the AMPK signaling pathway, suggesting a protective mechanism against oxidative damage in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-life galacto-oligosaccharides supplementation alleviates the small intestinal oxidative stress and dysfunction of lipopolysaccharide-challenged suckling piglets. Tian, S., Wang, J., Gao, R., et al.[2022]

A case series involving 6 mothers (4 pregnant and 2 lactating) revealed that they experienced anaphylactic reactions after consuming milk formula containing galacto-oligosaccharides (GOS), highlighting a potential allergy risk in atopic individuals.

All subjects had pre-existing atopy and positive skin prick tests to GOS, suggesting that GOS may pose an allergenic risk, particularly in sensitive populations, despite normal neonatal outcomes following the reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual cause of food-induced anaphylaxis in mothers. Soh, JY., Chiang, WC., Huang, CH., et al.[2023]

In a study involving 46 term infants, the addition of acidic oligosaccharides (AOS) to infant formula did not significantly alter the intestinal flora compared to a control group, indicating that AOS alone may not impact gut microbiota composition.

However, when combined with neutral oligosaccharides, the mixture significantly increased bifidobacteria and lactobacilli counts, while also improving stool consistency, suggesting that this combination could enhance digestive health without causing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acidic oligosaccharides from pectin hydrolysate as new component for infant formulae: effect on intestinal flora, stool characteristics, and pH. Fanaro, S., Jelinek, J., Stahl, B., et al.[2019]

Human milk oligosaccharides (HMO) may provide health benefits as prebiotics by modulating gut microbiota, but their manufacturing challenges have led to the exploration of alternatives like galacto-oligosaccharides (GOS).

GOS, produced from lactose, are being investigated for their ability to promote healthy gut bacteria and reduce intestinal infections, making them a promising addition to infant formulas and other food products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human milk and related oligosaccharides as prebiotics. Barile, D., Rastall, RA.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Effects of galacto-oligosaccharide ingestion on the mucosa-associated mucins and sucrase activity in the small intestine of mice. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Biological activity of galacto-oligosaccharides: A review. [2022]

3. Egypt pubmed.ncbi.nlm.nih.gov

Strain specificity of lactobacilli with promoted colonization by galactooligosaccharides administration in protecting intestinal barriers during Salmonella infection. [2023]

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

Galacto-oligosaccharides as infant prebiotics: production, application, bioactive activities and future perspectives. [2023]

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

Early-life galacto-oligosaccharides supplementation alleviates the small intestinal oxidative stress and dysfunction of lipopolysaccharide-challenged suckling piglets. [2022]

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

An unusual cause of food-induced anaphylaxis in mothers. [2023]

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

Acidic oligosaccharides from pectin hydrolysate as new component for infant formulae: effect on intestinal flora, stool characteristics, and pH. [2019]

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

Human milk and related oligosaccharides as prebiotics. [2018]