High Arabinose Diet for Gut Bacteria

(FEEDMe Trial)

Overseen By Jennifer Smilowitz, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must not be taking: Antibiotics, Biologics, Weight loss meds, others

Disqualifiers: Pregnancy, Restrictive diets, GI conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to refrain from changing their current medication regimen during the study period, meaning you should not start or stop any medications while participating.

What data supports the effectiveness of the high arabinose diet treatment for gut bacteria?

Research shows that L-arabinose, a component of the high arabinose diet, can inhibit colitis (inflammation of the colon) by positively affecting gut bacteria in mice. Additionally, arabino-oligosaccharides from sugar beet pectin, which are related to arabinose, have been found to promote the growth of beneficial gut bacteria in human studies. ^{1 2 3 4 5}

Is a high arabinose diet safe for humans?

Research suggests that L-arabinose and related compounds like pectin are generally safe for human consumption, with no adverse effects reported at certain doses. However, d-arabinose showed some toxicity in rats, indicating that more studies are needed to confirm its safety as a food ingredient. ^{5 6 7 8 9}

How does the high arabinose diet treatment differ from other treatments for gut bacteria?

The high arabinose diet is unique because it involves L-arabinose, a sugar that selectively inhibits intestinal sucrase (an enzyme that breaks down sucrose) and modulates gut microbiota, potentially offering a novel way to influence gut bacteria and manage blood sugar levels. ^{1 8 9 10 11}

What is the purpose of this trial?

The FEEDMe Study is a single-group, open label pilot study exploring how diverse, commercially available foods rich in arabinose influence the gut microbiome in adults from diverse populations.

Research Team

Jennifer Smilowitz, PhD

Principal Investigator

University of California, Davis

Eligibility Criteria

Healthy adults aged 18-50 who eat regularly, live close to specified locations, and have a BMI of 18.5-34.9 can join this study on diet and gut health. They must be willing to change their diet, avoid certain medications, and not travel during the study. Pregnant women or those with recent illnesses or digestive issues cannot participate.

Inclusion Criteria

Speaks, writes, and understands English

Consumes food at least three times per day

Willingness to refrain from certain medications and supplements

Exclusion Criteria

I have recently used antibiotics or biologic drugs.

I plan to travel during the study period.

Excessive alcohol, tobacco, or drug use

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Lead-in

Participants enter a 15-day lead-in period with a low arabinose diet and collect a baseline stool sample

2 weeks

1 visit (in-person)

Intervention

Participants consume study-provided high-arabinose foods

2.5 weeks

1 visit (in-person), 1 visit (virtual)

Follow-up

Participants refrain from consuming specific foods and are monitored for changes in gut microbiota

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• High arabinose diet

Trial Overview The FEEDMe Study is testing how foods high in arabinose affect the gut microbiome over an 18-day period. Participants will consume provided foods rich in this sugar while researchers monitor changes in their gut bacteria through stool samples.

Participant Groups

Group I: Pre, during and post high arabinose foods intake Experimental Treatment 1 Intervention

All individuals will enter a lead-in period consisting of a low arabinose diet, then they will consume a high arabinose diet and then back to the low arabinose diet.

High arabinose diet is already approved in United States, European Union for the following indications:

Approved in United States as L-arabinose for:

• Flavor enhancer
• Flavoring agent or adjuvant

Approved in European Union as L-arabinose for:

• Food additive
• Flavoring substance

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

L-arabinose selectively inhibits intestinal sucrase activity in an uncompetitive manner, which helps to reduce blood glucose levels after sucrose ingestion, as shown in mouse studies.

In vivo experiments demonstrated that L-arabinose effectively suppresses postprandial glycemic responses, with a significant effect observed for up to 3 weeks after sucrose loading, indicating its potential as a dietary intervention for managing blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals. Seri, K., Sanai, K., Matsuo, N., et al.[2019]

Increasing dietary levels of D-xylose or L-arabinose in chicks led to a significant decrease in weight gain and feed efficiency, indicating that higher levels of these sugars may negatively impact chick performance.

D-xylose and L-arabinose showed dose-related values for metabolizable energy, with D-xylose providing higher energy content at certain levels, while both sugars increased water intake and affected cecal size, suggesting potential implications for digestion and nutrient absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional implications and metabolizable energy value of D-xylose and L-arabinose in chicks. Schutte, JB.[2020]

Lower molecular weight arabino-oligosaccharides significantly stimulate the growth of beneficial gut bacteria, particularly bifidobacteria, suggesting their potential as effective prebiotics.

The study indicates that arabino-oligosaccharides, derived from sugar beet pulp, can enhance gut health by promoting beneficial bacteria while reducing harmful Clostridia, highlighting their value as a renewable resource in nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the human gut microflora. Al-Tamimi, MA., Palframan, RJ., Cooper, JM., et al.[2022]

In a study using a mouse model of colitis, l-arabinose was found to significantly reduce inflammation and colitis symptoms by inhibiting specific inflammatory pathways (p38-/p65-dependent activation).

The beneficial effects of l-arabinose were linked to its ability to modulate gut microbiota, suggesting it could be a promising functional food or therapeutic option for improving intestinal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

l-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice. Li, Y., Pan, H., Liu, JX., et al.[2019]

The study successfully separated arabino-oligosaccharides from sugar beet pectin into different fractions based on their feruloyl substitution and chain length, confirming the presence of bioactive compounds through advanced analytical techniques.

In vitro fermentation tests with samples from 6 healthy volunteers showed that both feruloylated and nonferuloylated long-chain arabino-oligosaccharides effectively stimulated the growth of beneficial bifidobacteria without promoting harmful bacteria like Clostridium difficile, suggesting their potential as prebiotic ingredients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feruloylated and nonferuloylated arabino-oligosaccharides from sugar beet pectin selectively stimulate the growth of Bifidobacterium spp. in human fecal in vitro fermentations. Holck, J., Lorentzen, A., Vigsnæs, LK., et al.[2018]

Pectin (E 440i) and amidated pectin (E 440ii) are considered safe as food additives, with no adverse effects reported in studies involving high doses, including a chronic toxicity study in rats at 5,000 mg/kg body weight per day.

The European Food Safety Authority concluded that these substances do not pose a safety concern for the general population, and there is no need for a specific acceptable daily intake (ADI) due to their extensive fermentation in the gut and lack of absorption intact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-evaluation of pectin (E 440i) and amidated pectin (E 440ii) as food additives. Mortensen, A., Aguilar, F., Crebelli, R., et al.[2023]

The acute toxicity study in rats revealed that the lethal dose (LD50) of d-arabinose is 12.1 g/kg for males and 11.6 g/kg for females, indicating a significant level of toxicity.

In a short-term toxicity test, rats experienced diarrhea at a 5% dietary inclusion of d-arabinose, suggesting that the maximum safe amount is likely below this level, which is higher toxicity compared to another rare sugar, d-psicose, that showed no toxicity at 10%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity of d-Arabinose in Male and Female Rats]. Higaki, S., Matsuo, T.[2019]

In a mouse model of type 2 diabetes, L-arabinose supplementation at a low dose of 20 mg/kg body weight per day significantly improved symptoms of diabetes, including reduced blood glucose levels and better pancreatic function, compared to a control group.

L-arabinose also positively influenced gut microbiota by decreasing the ratio of Firmicutes to Bacteroidetes, suggesting it may help restore gut health in diabetic conditions, making it a promising candidate for preventing or treating type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of L-arabinose by hypoglycemic and modulating gut microbiome in a high-fat diet- and streptozotocin-induced mouse model of type 2 diabetes mellitus. Shen, D., Lu, Y., Tian, S., et al.[2022]

L-arabinose has an apparent ileal digestibility of about 70% in pigs, indicating that a significant portion of this sugar is absorbed in the small intestine.

Increasing dietary levels of L-arabinose led to higher urinary excretion rates, with up to 14.7% of consumed L-arabinose appearing in urine at the highest dietary level, while also causing a decrease in faecal digestibility and nitrogen retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional implications of L-arabinose in pigs. Schutte, JB., de Jong, J., van Weerden, EJ., et al.[2019]

L-Arabinose, a five-carbon sugar found in pectin, is an important monomer for fermentation, yet it has been largely overlooked compared to D-xylose, which is more commonly studied.

Saccharomyces cerevisiae is identified as the best candidate for engineering to ferment L-arabinose into ethanol, suggesting that more research on this sugar and pectin-rich biomass could lead to valuable biofuel production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Engineering for Improved Fermentation of L-Arabinose. Ye, S., Kim, JW., Kim, SR.[2019]

Escherichia coli O157:H7 can metabolize l-arabinose derived from plant cell walls, indicating its ability to utilize this sugar during colonization of plants like spinach and lettuce.

The study found that while the deletion of certain genes (araBAD) did not affect the bacteria's ability to colonize plants, the presence of plant polysaccharides induced the expression of other genes (araA), highlighting a unique metabolic adaptation compared to other plant-associated microbes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of l-arabinose metabolism for Escherichia coli O157:H7 in edible plants. Crozier, L., Marshall, J., Holmes, A., et al.[2023]

References

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

L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Nutritional implications and metabolizable energy value of D-xylose and L-arabinose in chicks. [2020]

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

In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the human gut microflora. [2022]

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

l-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice. [2019]

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

Feruloylated and nonferuloylated arabino-oligosaccharides from sugar beet pectin selectively stimulate the growth of Bifidobacterium spp. in human fecal in vitro fermentations. [2018]

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

Re-evaluation of pectin (E 440i) and amidated pectin (E 440ii) as food additives. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Toxicity of d-Arabinose in Male and Female Rats]. [2019]

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

Effects of L-arabinose by hypoglycemic and modulating gut microbiome in a high-fat diet- and streptozotocin-induced mouse model of type 2 diabetes mellitus. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Nutritional implications of L-arabinose in pigs. [2019]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Metabolic Engineering for Improved Fermentation of L-Arabinose. [2019]

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

The role of l-arabinose metabolism for Escherichia coli O157:H7 in edible plants. [2023]