The Influence of Oxalate on Gut Microbiota: A Two-Way Street

Mar 24, 2024 | Detox, Diet, Digestive/Urinary, Evidence Based, Oxalate, Science-Based, Wellness

In a recent presentation, Dr. Aaron Miller of the Cleveland Clinic shared groundbreaking findings about oxalates, their interaction with the microbiome, and bile acids, drawing attention from Susan Owens and members who had the opportunity to engage in a Q&A session.

I also did a video on the implications of oxalate and dysbiosis.

Notably, Dr. Miller’s research unveiled that diets high in fat and sugar negatively affect the oxalate-degrading capabilities of the microbiome, similarly to the impact of antibiotics. A significant discovery was the prevalent involvement of lipids in this process.

Exploring the Unique Gut Microbiota of Neotoma Albigula Rats

A fascinating study focused on the Neotoma albigula rats, known for their ability to consume a high-oxalate diet without suffering adverse effects. This capability is particularly intriguing given that mammals typically lack the enzymes necessary to break down oxalates, suggesting that these rats possess a unique gut microbiota adept at managing oxalate digestion.

Key Insights from the Study:

  1. Oxalate Tolerance: Through controlled dietary experiments, researchers sought to identify the threshold of oxalate tolerance in Neotoma albigula rats. By gradually increasing the dietary oxalate up to 12% of the diet’s mass, they aimed to observe at what point, if any, the rats would exhibit signs of oxalate toxicity.
  2. Gut Microbiota’s Role: Remarkably, the study revealed that the gut microbiota of these rats is capable of degrading approximately 100% of the ingested oxalate, even when oxalate constituted as much as 12% of their diet. This finding underscores the exceptional efficiency of the rats’ gut microbiota in handling high levels of oxalate.
  3. No Threshold Reached: The experiments demonstrated that the Neotoma albigula rats never reached their threshold for oxalate tolerance within the tested ranges. This indicates that their unique gut microbiota enables them to safely consume significantly higher amounts of oxalate than would be possible for other mammals, highlighting an extraordinary adaptation.

Oxalate’s Impact on Gut Microbiota Diversity in Neotoma Albigula Rats

Continuing the exploration into Neotoma albigula rats’ unique dietary habits, further experiments revealed fascinating insights into how increased dietary oxalate affects the diversity of their gut microbiota.

Key Findings:

  1. Diversity Increase: The study showed that elevating dietary oxalate levels led to a notable increase in the diversity of bacterial species within the gut microbiota. This suggests that oxalate plays a significant role in enhancing microbiota complexity.
  2. Beneficial for Microbiota: The proliferation of diverse bacterial species upon higher oxalate intake indicates that oxalate may not only be tolerable but beneficial for the gut ecosystem of Neotoma albigula rats. The presence of oxalate seems to create an environment where even rare bacterial taxa can thrive and become more prevalent.
  3. Detection Through Sequencing: The increase in bacterial diversity and the emergence of rare taxa with higher oxalate diets were detectable through advanced sequencing techniques. This points to the intricate relationship between diet and gut microbiota composition, which can be unveiled through modern genetic sequencing methods.


These results underscore the intricate interactions between diet and gut microbiota. In the case of Neotoma albigula rats, the addition of oxalate to their diet doesn’t just challenge their gut microbiota; it enriches it, allowing for a more diverse bacterial population. This adaptability could offer insights into potential dietary strategies for managing gut microbiota diversity in other species, including humans, highlighting the importance of dietary components in shaping microbiota health and diversity.

Fecal transplant study

A fascinating study utilizing fecal transplants from wood rats to lab rodents offers some insights. Lab rodents, typically lacking oxalate-degrading bacteria, were given fecal transplants to see if this would alter their ability to degrade oxalate. Prior to the transplant, all rats excreted similar levels of urinary oxalate. Post-transplant, those receiving the fecal transplant showed a significant reduction in urinary oxalate compared to the control group, which did not receive any transplant. This experiment included groups receiving VSL #3 (a known probiotic mixture) and isolated oxalate-degrading bacteria from wood rats, alongside the fecal transplant group.

Interestingly, after a period of no oxalate intake (a washout period), followed by reintroduction to an oxalate-rich diet, the group that received the fecal microbial transplant demonstrated the best oxalate degradation capability. In contrast, the control group, which did not receive any transplant, had the highest levels of oxalate. This clearly demonstrates the dual influence where the gut microbiota affects oxalate levels and vice versa.

The study underscores the complex interplay between our diet, antibiotics, and the microbiome in maintaining oxalate homeostasis. It reveals that many species within the gut microbiota are responsible for this balance, offering new perspectives on managing oxalate levels through gut health. This breakthrough suggests potential dietary or probiotic interventions to manage conditions related to oxalate imbalance, such as kidney stones, by modulating the gut microbiome.

Other findings

Dr. Miller highlighted a detrimental correlation between dietary oxalates and bile acid levels, impacting the production of both primary and secondary bile acids. His research found a diverse presence of oxalate-degrading bacteria across various taxa, alongside an observed growth in specific bacteria when exposed to high-oxalate diets. This exposure, he noted, could integrate into and escalate the risk of developing atherosclerotic plaque.

Towards the end of his presentation, Dr. Miller emphasized the vulnerability caused by the absence of certain bacteria that produce short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate. Moreover, oxalate was shown to promote the growth of microorganisms that utilize formate, aligning with Masterjohn’s June 2023 article that delineates two phases in the breakdown of oxalate: the initial phase generating formate, a toxin, via biotin, and a second phase that requires non-methylated folate among other nutrients for formate decomposition.

An intriguing aspect of Dr. Miller’s findings is the varied impact of oxalate on individuals, affecting different organs such as the gallbladder, kidneys, eyes, ears, and skin in diverse ways, underscoring the personalized nature of its effects.

Oxalates, often vilified for their potential to form kidney stones, have a more complex relationship with our body, particularly the gut microbiota. Surprisingly, increased levels of oxalate can enrich the diversity of species within the gut microbiome. This enrichment allows for the proliferation of rare strains, suggesting oxalates may benefit certain microbial communities in our gut. But how does this relationship play out in terms of oxalate degradation, and can altering the gut microbiota affect how our body handles oxalate?

The Impact of Diet and Antibiotics on Oxalate Metabolism and Atherosclerosis and Kidney Pathology

The delicate balance of oxalate metabolism in our bodies is significantly influenced by our diet and antibiotic use, with profound implications for our overall health. A compelling study reveals that both antibiotic use and a diet high in fats and sugars can detrimentally affect oxalate metabolism, leading to increased levels of urinary oxalate. This increase is attributed to a disruption in the network of gut bacteria responsible for maintaining oxalate homeostasis.

Further emphasizing the gut microbiota’s pivotal role in oxalate metabolism, the study underlines the potential consequences of human antibiotic consumption on this delicate balance. The research ventured into exploring oxalate-induced atherosclerosis using APOE knockout mice, a model renowned for atherosclerosis studies. The mice were divided into groups based on their diet (0% oxalate vs. high 3% oxalate) and antibiotic usage.

Comprehensive analyses were conducted on gut microbiota, kidney lipid profiles, plasma cytokines and oxalate levels, urea, and the presence of atherosclerotic plaque and renal calcification. Remarkably, exposure to both dietary oxalate and antibiotics significantly exacerbated atherosclerotic plaque formation. This was visually confirmed through polarized light microscopy, which highlighted the presence of calcium oxalate crystals within the atherosclerotic plaques. This finding presents a potential mechanism by which dietary oxalate, in conjunction with antibiotic use, promotes atherosclerosis through the integration of calcium oxalate into plaque formations.

Moreover, the study identified two distinct oxalate-related phenotypes affecting the kidneys. In the absence of antibiotics, kidney stones and ureter obstruction were prevalent. However, with antibiotic treatment, a more severe condition, oxalate nephropathy, emerged, characterized by widespread crystal formation throughout the kidney tissue.

This study not only underscores the interconnectedness of diet, antibiotic use, and oxalate metabolism but also illuminates how these factors contribute to the development of atherosclerosis and kidney pathologies. The findings advocate for a mindful approach to antibiotic usage and dietary choices to maintain optimal health and prevent disease progression.

The Complex Interplay of Oxalate, Gut Microbiota, and Kidney Health

Recent studies reveal the intricate relationship between oxalate intake, gut microbiota, and its consequential effects on kidney health and cardiovascular disease (CVD) risk factors. Oxalate, a compound found in many foods, has been shown to influence lipid profiles associated with CVD, especially when combined with antibiotic use. This relationship is further complicated by the impact of oxalate on bile acid production and the gut-liver axis.

Bile Acids and Oxalate: Bile acids, essential for lipid metabolism, exist in two forms: primary bile acids produced by the liver and secondary bile acids transformed by gut bacteria. Oxalate affects liver activity by altering primary bile acid levels, but it also influences secondary bile acids through its effects on gut bacteria. Remarkably, while oxalate alone can increase bile acid levels, these benefits are negated when antibiotics are introduced, wiping out essential gut microbiota.

Cholesterol, Triglycerides, and Glucose Tolerance: The study demonstrated that oxalate’s interaction with antibiotics led to a significant increase in plasma cholesterol levels, likely due to changes in gut microbiota. Furthermore, this combination also worsened glucose tolerance, an important marker for cardiac health and atherosclerosis risk.

Oxalate’s Impact on Liver and Mitochondrial Function: A notable finding of the research is oxalate’s impact on liver activity and mitochondrial function. Oxalate exposure led to an increase in liver gene expression related to mitochondrial activity, suggesting that oxalate directly targets liver mitochondria. This effect varied among different mice, with some showing beneficial responses to oxalate, while others exhibited inhibited bacterial adaptability.

Microbial Metabolites and Hepatic Response: The study also explored how microbial metabolites produced due to oxalate exposure influence liver activity. In Swiss Webster mice, these metabolites resulted in decreased liver activity, yet in N abligula mice, the gut microbiota mitigated the negative effects of oxalate on liver and gut health through a host-independent mechanism.

Oxalate and Microbial Diversity: Interestingly, oxalate exposure stimulated a diverse range of microorganisms without significantly altering their metabolic output, indicating metabolic redundancy among different taxa. This includes stimulation of oxalate-degrading bacteria like Oxalobacter formigenes and Alistipes spp, which possess genes capable of degrading oxalate into formate and CO2.

Conclusions: This research sheds light on the complex interplay between dietary oxalate, gut microbiota, and its broad implications for liver and kidney health. By influencing bile acid production, lipid profiles, and mitochondrial function, oxalate intake has far-reaching consequences for metabolic health and disease risk. These findings highlight the importance of considering the gut microbiota’s role in dietary compound metabolism and its potential impact on the body’s physiological processes.

The Vital Role of Oxalate Metabolism in the Gut Microbiome

Recent research highlights the significance of oxalate metabolism within the human gut microbiota, emphasizing that 35% of the genomes extracted from this microbiota contain at least one oxalate-degrading gene. This capability is crucial for bacterial survival in the gut, underlining the importance of metabolic redundancy and cooperation among various species.

Key Findings on Oxalate Metabolism and Bacterial Species:

  1. Metabolic Redundancy: Eight species pivotal for oxalate metabolism were identified, showcasing a variety of bacteria capable of degrading oxalate, albeit dependent on the presence of formate in the media.
  2. Diverse Bacterial Groups: These species were categorized into four groups, with Oxalobacter formigenes standing out for its exceptional oxalate degradation capability. The other groups include commensal bacteria, bacteria without O. formigenes (demonstrating the ecosystem’s metabolic redundancy), and those specifically responsive to oxalate degradation.
  3. Formate’s Role: The presence of oxalate significantly influences formate metabolism, with microbial transplants showing a notable reduction in urinary oxalate levels. This indicates a cooperative metabolic relationship between oxalate metabolism and formate production.

Impact on Organ Health:

The study further explored how oxalate metabolism affects various organs, revealing that microbial metabolism not only is driven by redundancy but also significantly benefits organ health through metabolic cooperation. Key improvements were observed in:

  • Reduction of renal calcium oxalate deposition, mitigating the risk of kidney stones.
  • Alleviation of colitis, suggesting a protective effect against gut inflammation.
  • Reduction in oxalate-induced cardiac fibrosis, indicating a protective role for the heart and vascular system.

Moreover, microbial transplants from oxalate-metabolizing bacteria led to lower fecal oxalate levels, showcasing the collective efficacy of these bacteria in reducing oxalate’s adverse effects.

My take on this study 

This study underscores the importance of maintaining optimal gut health through strategic dietary choices, prudent use of antibiotics, and the incorporation of specific probiotics. It highlights how dietary diversity can enrich gut microbiota diversity, which is crucial for overall health and the effective degradation of compounds like oxalates. The research advises against unnecessary antibiotic use, which can disrupt gut microbial balance and reduce oxalate metabolism, leading to increased urinary oxalate levels. Emphasizing the role of spore-based probiotics, the study suggests these can promote a more diverse and resilient gut microbiome. Moreover, it warns of the long-term detrimental effects of exogenous chemicals, specifically pesticides and herbicides like glyphosate, on gut health. This comprehensive approach to gut health, focusing on diet, careful antibiotic use, and avoidance of harmful chemicals, is pivotal for maintaining the gut microbiota’s crucial functions, including its influence on various organ systems and its role in metabolic redundancy and cooperation.


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