Gut Bacteria for Kidney Stones

Recruiting at 1 trial location

Overseen By Demond Wiley

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must be taking: Thiazides, Citrate, Allopurinol

Must not be taking: Immunosuppressive medication

Disqualifiers: Chronic kidney disease, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this trial is to test if colonization with the gut bacteria Oxalobacter formigenes leads to a reduction in urinary oxalate excretion in patients with calcium oxalate kidney stone disease. The study will recruit adult participants with a history of calcium oxalate kidney stones who are not colonized with Oxalobacter formigenes. Participants will * ingest fixed diets containing low and moderately high amounts of oxalate for 4 days at a time * collect urine, blood and stool samples during the fixed diets * ingest a preparation of live Oxalobacter formigenes to induce colonization with Oxalobacter formigenes

Will I have to stop taking my current medications?

The trial requires participants to stop taking supplements like vitamins, calcium, and probiotics for 2 weeks before and during the diet phases. If you are on medications for kidney stone prevention, you must be on a stable dose for at least 2 weeks before and during the study.

What data supports the effectiveness of the treatment Oxalobacter formigenes for kidney stones?

Research suggests that Oxalobacter formigenes, a type of gut bacteria, can help reduce the risk of kidney stones by breaking down oxalate, a key component of most kidney stones. Studies have shown that having this bacteria in the gut is linked to lower levels of oxalate in urine, which may help prevent the formation of calcium oxalate stones. ^{1 2 3 4 5}

Is Oxalobacter formigenes safe for humans?

The research does not provide specific safety data for Oxalobacter formigenes, but it is a naturally occurring gut bacterium found in healthy individuals, suggesting it is generally safe. ^{1 2 3 6 7}

How does the treatment Oxalobacter formigenes differ from other treatments for kidney stones?

Oxalobacter formigenes is unique because it is a type of bacteria that naturally lives in the gut and breaks down oxalate, a key component of most kidney stones, potentially reducing their formation. Unlike traditional treatments that may focus on managing symptoms or surgically removing stones, this approach targets the root cause by altering gut bacteria to decrease oxalate levels in the body. ^{1 3 5 6 7}

Research Team

Sonia Fargue, M.D., Ph.D.

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

Adults with a history of calcium oxalate kidney stones who currently do not have the gut bacteria Oxalobacter formigenes. Participants will need to follow strict diets and provide urine, blood, and stool samples.

Inclusion Criteria

I am willing to stop taking vitamins, minerals, and supplements for 2 weeks before and during the diet phases.

Body Mass Index > 18.5 kg/m2

Willing to ingest fixed diets

Exclusion Criteria

I have been diagnosed with primary hyperoxaluria.

Pregnancy or breast-feeding

My kidney function is severely reduced.

Timeline

Screening and Pre-colonization

Participants are screened for eligibility to participate in the trial, including stool colonization testing, blood complete metabolic profile, 24-hr urine specimens collected at home on self-selected diets and anthropometric measurements.

2-4 weeks

1 visit (in-person) for screening, home collections

Colonization and Post-colonization

Participants are colonized with Oxalobacter formigenes and follow a fixed diet to measure urinary oxalate excretion before and after colonization.

2 months

Multiple visits for sample collection and diet adherence

Follow-up

Participants are monitored every 6 months to assess sustainability of colonization, provide a stool sample, and answer a questionnaire. A 24-hr urine collection is requested once a year.

4 years

Biannual visits (in-person or virtual), annual urine collection

Treatment Details

Interventions

• Oxalobacter formigenes

Trial Overview The trial is testing whether introducing Oxalobacter formigenes into patients can lower urinary oxalate levels. It involves fixed diets with varying oxalate levels before and after colonization with the bacteria.

Participant Groups

Group I: colonization with Oxalobacter formigenes Experimental Treatment 5 Interventions

Colonization with a live preparation of Oxalobacter formigenes, strain OxCC13.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Transplanting human feces along with the O. formigenes strain into mice successfully established stable colonization of these bacteria for at least 8 weeks, indicating a potential model for studying their effects on kidney stone risk.

The humanization process significantly altered the gut microbiome of the mice, suggesting that O. formigenes can integrate into and modify the intestinal microbial community, which may help in identifying effective strains for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization. Pebenito, AM., Liu, M., Nazzal, L., et al.[2020]

The presence of the bacterium Oxalobacter formigenes in the intestine can help reduce urinary oxalate levels, which lowers the risk of developing calcium oxalate kidney stones.

The genome sequence of a specific strain, Oxalobacter formigenes SSYG-15, was obtained from a healthy individual, providing valuable genetic information that could enhance our understanding of its beneficial effects on kidney stone prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome Sequence of Oxalobacter formigenes Strain SSYG-15. Sun, NY., Gao, Y., Yu, HJ.[2020]

Oxalobacter formigenes, a gut bacterium, helps break down oxalate, which can lower urinary oxalate levels and potentially reduce the risk of kidney stones, particularly those made of calcium oxalate.

The review highlights the impact of antibiotics on the colonization of Oxalobacter formigenes and suggests that probiotics and whole microbial communities could be explored as possible treatments for kidney stone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the microbiome in kidney stone formation. Mehta, M., Goldfarb, DS., Nazzal, L.[2018]

In a study of 103 patients with calcium oxalate stone disease, 45.6% were found to have intestinal colonization of Oxalobacter formigenes, which is associated with lower urinary oxalate levels.

The presence of O. formigenes in the gut was linked to a significant decrease in urinary oxalate excretion, suggesting that this bacterium plays a crucial role in maintaining oxalate balance and may help reduce the risk of kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary oxalate levels and the enteric bacterium Oxalobacter formigenes in patients with calcium oxalate urolithiasis. Kwak, C., Kim, HK., Kim, EC., et al.[2022]

In a study using male Sprague-Dawley rats with induced hyperoxaluria, treatment with the bacterium Oxalobacter formigenes significantly reduced urinary oxalate levels within just 2 days, with greater reductions observed at higher doses.

The probiotic treatment was found to be safe, as the rats showed no signs of toxicity or health issues, suggesting that O. formigenes could be a promising option for managing calcium oxalate kidney stone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. Sidhu, H., Allison, MJ., Chow, JM., et al.[2017]

In a study of 76 children and adolescents with calcium oxalate urolithiasis, only 27.6% were colonized with the bacterium Oxalobacter formigenes, similar to the 26% colonization rate in healthy controls.

Children with calcium urolithiasis who were colonized with O. formigenes had significantly lower urinary oxalate excretion compared to those who were not colonized, suggesting that the absence of this bacterium may contribute to higher oxalate levels and increased risk of kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal colonization with Oxalobacter formigenes and its relation to urinary oxalate excretion in pediatric patients with idiopathic calcium urolithiasis. Sikora, P., Niedźwiadek, J., Mazur, E., et al.[2018]

This study found no causal link between the gut bacterium Oxalobacter formigenes and the formation of kidney stones, suggesting that its presence does not significantly influence kidney stone development.

However, other gut microbiota, such as certain genera and families, were identified as either protective or risk factors for kidney stones, indicating a more complex relationship that warrants further investigation using advanced research methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Causal relationship between kidney stones and gut microbiota contributes to the gut-kidney axis: a two-sample Mendelian randomization study. Liu, M., Zhang, Y., Wu, J., et al.[2023]

References

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

Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization. [2020]

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

Genome Sequence of Oxalobacter formigenes Strain SSYG-15. [2020]

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

The role of the microbiome in kidney stone formation. [2018]

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

Urinary oxalate levels and the enteric bacterium Oxalobacter formigenes in patients with calcium oxalate urolithiasis. [2022]

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

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. [2017]

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

Intestinal colonization with Oxalobacter formigenes and its relation to urinary oxalate excretion in pediatric patients with idiopathic calcium urolithiasis. [2018]

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

Causal relationship between kidney stones and gut microbiota contributes to the gut-kidney axis: a two-sample Mendelian randomization study. [2023]