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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of two types of prebiotics—compounds that promote the growth of beneficial gut bacteria—in healthy adults. Participants will use either standard Galacto-oligosaccharides (GOS), enriched Humanized Galacto-oligosaccharides (hGOS), or a placebo to assess their effects on gut health, inflammation, and digestive comfort. The study aims to determine if these prebiotics can boost beneficial gut bacteria and improve gut function. It seeks non-smoking adults who can commit to a 4-week trial, track their food intake, and provide blood and stool samples. As an unphased trial, this study offers a unique opportunity to advance scientific understanding of gut health and prebiotics.

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.

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

A previous study demonstrated that humanized galacto-oligosaccharides (hGOS) are safe and positively affect healthy gut bacteria. This study tested the prebiotic in mice and confirmed its safety. Research has also shown that GOS, similar to hGOS, is very safe. The main side effect of GOS is temporary bloating, which is not considered serious. These findings suggest that both hGOS and GOS are generally well-tolerated in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they involve innovative prebiotics designed to improve gut health. Unlike traditional prebiotics, which include ingredients like fiber supplements and inulin, these treatments use galacto-oligosaccharides (GOS) and a special version called humanized galacto-oligosaccharides (hGOS). The hGOS is enriched with lactosamine, which is thought to more closely mimic the beneficial sugars found in human milk, potentially offering unique benefits for the gut microbiome. This novel approach aims to enhance the diversity and balance of gut bacteria more effectively, which could lead to better gut health outcomes.

What evidence suggests that this trial's treatments could be effective for gut health?

This trial will compare the effects of humanized galacto-oligosaccharides (hGOS) and standard galacto-oligosaccharides (GOS) on gut health. Research has shown that both hGOS and GOS can improve gut health. Studies have found that GOS increases the number of beneficial bacteria in the gut, particularly Bifidobacterium, which aids digestion and may alleviate issues like lactose intolerance. Similarly, hGOS safely adjusts the balance of bacteria in the digestive system. Both types of GOS are linked to reducing gut inflammation and strengthening the gut lining, maintaining a healthy digestive system. These findings support the potential of GOS and hGOS to enhance gut health. ^{2 6 7 8 9}

Who Is on the Research Team?

Sylvia Becker-Dreps, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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.

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

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

Exclusion Criteria

I am under 18 or over 55 years old.

Pregnant or breastfeeding

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11366710/

A double-blind intervention trial in healthy women ... Multiple studies have demonstrated a positive impact of GOS on gut microbiota composition and activity, so-far mainly related to Bifidobacterium ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0023643824015743

Effects of galactooligosaccharides (GOS) on the gut ... The findings suggest that GOS enhances the presence of commensal Bifidobacteria and potentially alleviates LI symptoms.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2161831324000978

Galacto-Oligosaccharides and the Elderly Gut GOS has been proven effective in reducing the incidence and severity of infections, including respiratory infections in infants and children, rotavirus (RV)- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12388037/

Galacto-Oligosaccharides Exert Bifidogenic Effects at ... Results: The GOS were rapidly fermented and significantly increased beneficial Bifidobacterium species (B. adolescentis, B. bifidum, and B.

5. microbiomejournal.biomedcentral.com microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00980-0

The pleiotropic effects of prebiotic galacto-oligosaccharides ... In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8058378/

Safety and Modulatory Effects of Humanized Galacto ... Our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo.

7. scholars.duke.edu scholars.duke.edu/individual/pub1557914

Safety and Modulatory Effects of Humanized Galacto ... Complex dietary carbohydrate structures including β(1-4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract ...

8. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jafc.4c03881

and Galacto-Oligosaccharides in the Human Small Intestine We provide evidence on the resistances of GOS with specific β-linkages in the human intestine, supporting the development of GOS prebiotics that resist small ...

9. mdpi.com mdpi.com/2075-4426/10/4/161

Changes in the Gut Microbiome after Galacto- ... On the contrary, the side effect of taking excessive GOS is only temporary bloating; thus, GOS is considered to be very safe [11,12]. Previous studies focused ...