The microbiome is the collective genomes of microbes (bacteria, bacteriophage, fungi, protozoa, and viruses) that live inside and on the human body. The oxalobiome, on the other hand, is the collection of gut microbes involved in oxalate metabolism. It plays a significant role in kidney stone formation. High oxalate levels in the urine can contribute to the formation of calcium oxalate stones, the most common type of kidney stones. This blog will explore the oxalobiome, how it functions, and its impact on kidney stone development.
By Majd Isreb, MD, FACP, FASN, IFMCP
What is the Oxalobiome?
The oxalobiome comprises specific gut bacteria capable of breaking down dietary oxalate. The most notable of these bacteria include Oxalobacter formigenes, which utilizes oxalate as its energy source, reducing the amount absorbed into the bloodstream and subsequently excreted by the kidneys. Other members of the oxalobiome include Lactobacillus sp., Bifidobacterium sp., and Escherichia Coli. Understanding the composition and health of the oxalobiome is essential for assessing its role in preventing kidney stones.
Bowel Disease and Kidney Stone Formation
Research has shown that individuals with bowel diseases, such as inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis, have a higher risk of developing kidney stones. This connection is primarily due to fat malabsorption and changes in gut function that accompany these conditions.
In cases of chronic bowel inflammation, the absorption of fat can be impaired. Excess fat in the gut binds dietary calcium, making it less available to bind dietary oxalate. This leads to higher levels of unbound oxalate in the intestines. The excess oxalate can then be easily absorbed into the bloodstream and filtered by the kidneys, where it can bind with calcium to form calcium oxalate stones.
Additionally, chronic diarrhea, often associated with these bowel diseases, can lead to dehydration and reduced urine volume, further increasing the risk of kidney stone formation. Finally, the disruption in gut microbiota (dysbiosis) due to inflammation or medication use can also alter the balance of the oxalobiome, diminishing the body’s ability to metabolize dietary oxalate effectively and contributing to an increased risk of stone formation.
Antibiotic Exposure and Kidney Stone Formation
The use of antibiotics has been thought to increase the risk of kidney stone formation due to their impact on the gut microbiome. Antibiotics can disrupt the balance of beneficial bacteria in the gut, including those that form the oxalobiome, which is responsible for breaking down and metabolizing dietary oxalate.
In a study of 13 million children and adults from 1994 to 2015 in the United Kingdom, The Health Improvement Network (THIN) matched 25,981 patients with kidney stones to 259,797 controls and found an association between 12 classes of oral antibiotics and kidney stones. Sulfa-containing antibiotics had the highest risk for kidney stones.
Long-term or repeated courses of antibiotics can exacerbate this effect, making individuals more prone to kidney stone development. Additionally, the impact on gut health and the microbiome can persist for an extended period after antibiotic use, suggesting a lasting vulnerability to stone formation that should be considered in both medical and dietary planning.
It is essential to mention, though, that a recent study found that the perceived increased risk of symptomatic kidney stones with antibiotic use may be mainly due to both comorbidities and the prescription of antibiotics for urinary symptoms.
Join us to end the kidney disease epidemic
The Link Between Oxalobiome and Kidney Stones
When the gut’s oxalate-degrading bacteria are compromised, dietary oxalate absorption increases, elevating urinary oxalate levels. High urinary oxalate can bind calcium and crystallize to form calcium oxalate stones. Factors that disrupt the oxalobiome include antibiotic use, poor dietary habits, and gastrointestinal conditions that alter gut flora.
Studies have demonstrated that kidney stone formers have microbiome profiles different from those of non-stone formers. Stone formers exhibited lower fecal microbial diversity than controls. Three microbes, Faecalibacterium, Enterobacter, and Dorea, were significantly less represented in fecal samples of stone formers. Interestingly, the abundance of Oxalobacter was not different between the groups in this study.
The Effect of Oxalobiome on Urinary Citrate
Urinary citrate prevents kidney stone formation by acting as a natural inhibitor of stone development. Citrate binds to calcium in the urine, reducing the amount of free calcium available to form calcium oxalate or calcium phosphate stones. Additionally, citrate helps maintain an alkaline urine pH, further inhibiting the crystallization of stone-forming minerals.
Studies have shown that higher urinary citrate levels are associated with a reduced risk of kidney stones. Low citrate levels, a condition known as hypocitraturia, can be influenced by various factors, including diet, metabolic conditions, and certain medications. Increasing dietary intake of citrate-rich foods, such as citrus fruits, or using citrate supplements may help raise urinary citrate levels and thus provide a protective effect against kidney stones.
It appears that the oxalobiome also plays a role in increasing urinary citrate to decrease the risk of kidney stone formation further. In fact, urinary citrate increased by 31% from baseline at 1 week after fecal transplantation. Urinary calcium and oxalate also decreased significantly. Another study confirmed this.
The Role of Short-Chain Fatty Acids
A healthy gut microbiome can produce short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, through the fermentation of dietary fibers. These SCFAs play a vital role in maintaining gut health and influencing various physiological processes.
SCFAs have been shown to modulate the intestinal absorption of oxalate through their impact on gut permeability and the regulation of ion transport. By promoting a healthy gut barrier, SCFAs can reduce the passive paracellular absorption of oxalate (in between the cells), limiting its entry into the bloodstream. See the figure below.
Additionally, SCFAs can influence the expression of transport proteins involved in active cellular oxalate absorption, potentially decreasing the amount of oxalate that passes into the systemic circulation. This regulatory effect helps to maintain balanced oxalate levels, reducing the burden on the kidneys and lowering the risk of oxalate crystal formation, which is crucial for preventing kidney stones.
The production of SCFAs and their beneficial actions highlight the importance of a diverse and well-functioning gut microbiome for supporting kidney health and mitigating stone risk.
Join us to end the kidney disease epidemic
Can We Manipulate the Oxalobiome to Prevent Stones?
Probiotics and prebiotics may support a healthy oxalobiome, though more research is needed to confirm their efficacy in preventing kidney stones. Potentially, boosting Oxalobacter formigenes and other beneficial bacteria could be a therapeutic approach to managing kidney stone risk in susceptible individuals. However, studies on using probiotics to prevent kidney stones have been disappointing. This is likely due to the temporary effect of short-term probiotics on gut microbial diversity.
Integrative Tips for Supporting Oxalate Metabolism and Kidney Health
- Limit High-Oxalate Foods: Moderation is key; consider consulting with a healthcare provider for a diet tailored to kidney stone prevention. Remember that most urinary oxalate is actually produced inside the body by the liver from collagen metabolism.
- Hydration: Drinking plenty of water helps flush out oxalate before it can contribute to stone formation.
- Pre and Probiotics: Including prebiotic-rich foods such as fiber and resistant starch and probiotic-rich foods like kefir and sauerkraut may support overall gut health and, indirectly, the oxalobiome.
The Bottom Line on Oxalobiome and Kidney Stone Formation
The intricate link between gut health and kidney stone formation highlights the vital role of a balanced microbiome in maintaining kidney health. The oxalobiome, responsible for metabolizing dietary oxalate, underscores how specific gut bacteria can prevent excess oxalate absorption, ultimately reducing kidney stone risk. Factors such as antibiotic use, bowel diseases, and dietary habits can disrupt the balance of these beneficial bacteria, contributing to an increased likelihood of stone formation.
Supporting a healthy gut through dietary choices rich in both probiotics and prebiotics can be a powerful preventive strategy. Incorporating foods such as kefir, sauerkraut, chicory root, and garlic can help maintain a diverse and balanced gut environment. These dietary habits, coupled with hydration, an alkaline diet rich in citrate, and moderation of high-oxalate foods, offer an integrative approach to managing kidney stone risk.
