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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how consuming foods high in arabinose, a sugar found in plants, affects gut bacteria. Participants will alternate between a low arabinose diet and a high arabinose diet to observe changes in gut health. The trial seeks healthy adults who eat at least three times a day and can commit to study requirements, such as dietary changes and providing stool samples. As an unphased trial, this study offers a unique opportunity to contribute to scientific understanding of diet and gut health.

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 prior data suggests that a high arabinose diet is safe for adults?

Research has shown that L-arabinose, a sugar found in some foods, is generally safe for people. No harmful effects have been reported at certain intake levels, allowing most people to consume it without issues.

However, some animal studies suggest that excessive L-arabinose can disturb gut bacteria balance, leading to dysbiosis. In mice, a diet high in L-arabinose worsened certain infections.

It's important to note that humans are not mice, and the amounts used in these animal studies may differ from typical human consumption. Overall, current research suggests that foods containing L-arabinose are safe for humans when consumed in moderation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the high arabinose diet because it offers a fresh approach to enhancing gut health by specifically targeting gut bacteria. Unlike current treatments that often focus on probiotics or fiber supplements, this diet leverages arabinose, a naturally occurring sugar, to potentially alter the gut microbiome balance. The unique feature of this diet is its ability to shift the gut environment through dietary changes alone, which could lead to improved digestive health and possibly other systemic benefits without the need for pharmaceutical interventions.

What evidence suggests that a high arabinose diet is effective for influencing the gut microbiome?

Research has shown that consuming large amounts of arabinose, a sugar found in some plants, can alter the gut's bacterial composition. This sugar can increase beneficial bacteria like Bifidobacterium and boost short-chain fatty acids, which support gut health. L-arabinose might also help reduce body weight, blood pressure, blood sugar, and cholesterol. However, it could worsen infections from harmful bacteria like Salmonella in some cases. Overall, this diet may improve gut health, but its effects can vary among individuals. Participants in this trial will follow a regimen that includes a lead-in period with a low arabinose diet, followed by a high arabinose diet, and then return to a low arabinose diet to assess these effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Jennifer Smilowitz, PhD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/high-arabinose-diet-for-gut-bacteria-10d34

High Arabinose Diet for Gut Bacteria (FEEDMe Trial) In vivo experiments demonstrated that L-arabinose effectively suppresses postprandial glycemic responses, with a significant effect observed for up to 3 weeks ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1756464624000495

L-arabinose exerts probiotic functions by improving gut ... The results revealed that L-arabinose significantly altered the gut microbiome structure, particularly elevating Bifidobacterium and short-chain fatty acids ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6950088/

L-Arabinose Elicits Gut-Derived Hydrogen Production and ... L-arabinose administration for 6 weeks reduces body weight, blood pressure, blood glucose, triglycerides, total cholesterol, serum insulin, serum TNF-α and ...

4. journals.asm.org journals.asm.org/doi/10.1128/msystems.00522-24

Dietary L-arabinose-induced gut dysbiosis exacerbates ... Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.13991

Effects of L‐arabinose by hypoglycemic and modulating ... In this study, we found that low-dose (20 mg (kg bw)−1d-1) supplementation of L-arabinose significantly improved glucose intolerance and gut ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9455721/

Influence of Foods and Nutrition on the Gut Microbiome and ... High sugar intake is a hallmark of the Western diet. The link between high sugar intake and IBD was recently demonstrated in animal models of colitis. Short ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2161831322002885

Adaptation of the Gut Microbiota to Modern Dietary Sugars ... In this review, we discuss how gut microbes are affected by changes in the consumption of sugars and other sweeteners through transcriptional, abundance, and ...

8. cghjournal.org cghjournal.org/article/S1542-3565(21)01305-7/fulltext

Sugars and Gastrointestinal Health Sugar overconsumption is linked to a rise in the incidence of noncommunicable diseases such as diabetes, cardiovascular diseases, and cancer.