Dietary Fats for Gut Health

Overseen By Sean H. Adams, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must not be taking: Antibiotics, Weight-loss aids

Disqualifiers: Pregnancy, Diabetes, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain over-the-counter medications and dietary supplements during the run-in week and test day. If you are on prescription medications that could affect gut health or metabolism, you may need to stop taking them, but the protocol does not specify which ones.

What data supports the effectiveness of the treatment Sparking Gut Bacteria Production of Bioactive Xenolipids in Situ for gut health?

Research shows that lipids produced by gut bacteria can influence health by controlling inflammation and other cell functions. Additionally, dietary lipids can positively affect gut bacteria, which may improve metabolic health, suggesting potential benefits for gut health. ^{1 2 3 4 5}

How is the treatment Sparking Gut Bacteria Production of Bioactive Xenolipids different from other treatments for gut health?

This treatment is unique because it focuses on stimulating the production of bioactive xenolipids (special fats) directly in the gut by encouraging specific gut bacteria to produce them, which is different from other treatments that may not target the gut microbiome in this way. ^{6 7 8 9 10}

What is the purpose of this trial?

Long-chain cyclopropane fatty acids (CpFAs) are microbially-derived lipids (fats), some of which can be found in select foods and appear to be produced naturally in the gut from dietary fatty acid precursors. Some of these lipids appear to have signaling properties in the body's tissues, i.e., to help regulate cardiometabolic health. Thus, increasing the bioavailability of CpFAs in humans may have utility to improve management of blood sugar and blood lipids, or to mitigate or prevent non-alcoholic fatty liver disease (NAFLD). This study is a proof-of-principle experiment in 10 subjects, to feed dietary fats thought to enhance upper gut CpFA production. The latter will be monitored through post-meal blood and urine CpFA concentration measurements, as well as concentration in the stool.

Research Team

Sean H. Adams, PhD

Principal Investigator

University of California, Davis

Eligibility Criteria

This trial is for individuals with hyperlipidemia, which means they have high levels of fats in their blood. Participants should be willing to consume specific dietary fats and undergo sampling from inside the intestine using a pill-like device that will be swallowed.

Inclusion Criteria

I am 18-50 years old, with a BMI of 18.5-29.9, and can consent in English.

Exclusion Criteria

Allergy or aversion to any of the foods that will be studied and/or provided

I use tobacco or similar products and am not willing to stop for the study period.

I was hospitalized for heart disease or related conditions in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive dietary fats to enhance upper gut CpFA production, monitored through post-meal blood and urine CpFA concentration measurements

1 week

Daily visits for meal intake and sample collection

Follow-up

Participants are monitored for changes in CpFA concentrations in blood, urine, and stool

1 week

Treatment Details

Interventions

• Sparking Gut Bacteria Production of Bioactive Xenolipids in Situ

Trial Overview The study tests if eating certain dietary fats can boost gut bacteria's production of CpFAs—fats that may help manage blood sugar and lipids, potentially preventing or treating NAFLD. It involves monitoring CpFA levels in blood, urine, and intestinal samples after meals.

Participant Groups

Group I: Dietary fat with positive control supplement Experimental Treatment 1 Intervention

Dietary fat-containing meal plan with a specific supplement that may modify fat metabolism

Group II: Dietary fat with negative control supplement Experimental Treatment 1 Intervention

Dietary fat-containing meal plan with a specific supplement that should not modify fat metabolism

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

Fecal transplantation can be limited by the transfer of harmful living organisms, which increases the risk of infection, highlighting the need for safer therapeutic approaches.

Gut microbiota-derived lipids play a crucial role in regulating inflammation and other cellular functions, suggesting that these bioactive lipids could be harnessed for personalized therapies through metabolic engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipids from gut microbiota: pursuing a personalized treatment. Carneiro, PV., Montenegro, NA., Lana, A., et al.[2022]

A study screening 2250 human gut bacterial strains revealed that Blautia producta is particularly effective in reducing lipid accumulation and improving hyperlipidemia in mice fed a high-fat diet.

The active metabolite identified from Blautia producta, 12-methylmyristic acid (12-MMA), improves lipid levels and glucose metabolism by activating the G protein-coupled receptor 120 (GPR120), highlighting its potential as a therapeutic agent against metabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strain-level screening of human gut microbes identifies Blautia producta as a new anti-hyperlipidemic probiotic. Xu, W., Yu, J., Yang, Y., et al.[2023]

Solid lipid nanoparticles (SLNs) effectively protect phenolic compounds like rosmarinic acid during digestion, enhancing their bioavailability and allowing them to promote beneficial gut microbiota growth without inhibiting bacterial activity.

The study demonstrated that SLNs loaded with herbal extracts not only support the growth of beneficial bacteria but also increase the production of important fatty acids, indicating their potential as functional food ingredients that positively influence gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentation of bioactive solid lipid nanoparticles by human gut microflora. Madureira, AR., Campos, D., Gullon, B., et al.[2017]

Recent advances in sequencing technologies have highlighted the significant role of dietary lipids in shaping gut microbiota composition, which in turn affects the metabolic health of the host.

The review emphasizes that both dietary and endogenous lipids can influence gut health, suggesting their potential as prebiotic agents in medical foods or nutraceuticals, while also serving as indicators of gut health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Non-Polar Dietary and Endogenous Lipids on Gut Microbiota Alterations: The Role of Lipidomics. Tsiantas, K., Konteles, SJ., Kritsi, E., et al.[2022]

In patients with inflammatory bowel diseases (IBD), ineffective anti-TNF-α therapy was linked to an imbalance in gut bacteria and lower levels of palmitoleic acid (POA), which is crucial for gut health.

Dietary POA improved gut barrier function and enhanced the effectiveness of anti-TNF-α therapy in mouse models of IBD by promoting the growth of beneficial bacteria, specifically Akkermansia muciniphila, and reducing inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis. Chen, Y., Mai, Q., Chen, Z., et al.[2023]

A novel method called Bioorthogonal labeling-Sort-Seq-Spec (BOSSS) was developed to study how dietary sphingolipids, specifically sphinganine alkyne (SAA), interact with the gut microbiome, revealing that gut Bacteroides are primarily responsible for assimilating SAA.

The study found that Bacteroides and Bifidobacterium can metabolize dietary sphingolipids into dihydroceramides, highlighting their significant role in processing these lipids and suggesting important implications for diet-microbiome interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome. Lee, MT., Le, HH., Johnson, EL.[2023]

The study utilized targeted and untargeted lipidomics to analyze simulated intestinal chyme from an in vitro gut model, revealing that the gut microbiome significantly influences lipid profiles across different sections of the colon.

Key lipid classes, including phosphatidylcholines, sphingomyelins, and endocannabinoids, showed significant changes over time and between different gut compartments, indicating the dynamic nature of gut-derived lipids in regulating host metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamics of the Lipidome in a Colon Simulator. Kråkström, M., Dickens, AM., Alves, MA., et al.[2023]

In a study with high-fat diet-fed mice, glycerol monolaurate (GML) at a dose of 1,600 mg/kg significantly reduced body weight, visceral fat, and improved metabolic health indicators like hyperlipidemia and glucose homeostasis.

GML was found to positively influence gut microbiota by increasing Bifidobacterium pseudolongum, and its metabolic benefits were lost when antibiotics were used, highlighting the importance of gut bacteria in its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of the Gut Microbiota during High-Dose Glycerol Monolaurate-Mediated Amelioration of Obesity in Mice Fed a High-Fat Diet. Zhao, M., Jiang, Z., Cai, H., et al.[2021]

In a study of mice fed high and low linoleic acid soybean oil diets for 10 weeks, it was found that the gut microbiome significantly influences liver sphingolipid levels, regardless of the type of fat consumed.

While both conventional and germfree mice gained fat weight and consumed more calories on a high-fat diet, the specific fatty acid levels in the plasma were primarily determined by the diet, highlighting the complex interaction between diet and microbiome in fat metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil. Di Rienzi, SC., Johnson, EL., Waters, JL., et al.[2023]

Gut microbiota play a crucial role in influencing lipid levels in the intestines, as their presence reduces free cholesterol and increases phosphatidylcholine in the colon, based on a study using mass spectrometry on germfree and specific pathogen free mice.

The study also found that gut microbes inhibit the metabolism of polyunsaturated fatty acids (PUFAs) in the small intestine, leading to higher levels of important fatty acids like arachidonic and docosahexaenoic acid in germfree mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of gut microbiota on the intestinal lipidome of mice. Liebisch, G., Plagge, J., Höring, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Lipids from gut microbiota: pursuing a personalized treatment. [2022]

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

Strain-level screening of human gut microbes identifies Blautia producta as a new anti-hyperlipidemic probiotic. [2023]

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

Fermentation of bioactive solid lipid nanoparticles by human gut microflora. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Non-Polar Dietary and Endogenous Lipids on Gut Microbiota Alterations: The Role of Lipidomics. [2022]

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

Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis. [2023]

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

Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Dynamics of the Lipidome in a Colon Simulator. [2023]

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

Modulation of the Gut Microbiota during High-Dose Glycerol Monolaurate-Mediated Amelioration of Obesity in Mice Fed a High-Fat Diet. [2021]

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

The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil. [2023]

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

The effect of gut microbiota on the intestinal lipidome of mice. [2021]