According to the wikipedia entry for oxalobacter formigenes, “Quinolone, a broad-spectrum antibiotic, kills O. formigenes. If a person’s gastrointestinal (GI) tract lacks this bacterium, and therefore lacks the primary source for the oxalyl-CoA decarboxylase enzyme, then the GI tract cannot degrade dietary oxalates which on digestion get absorbed easily and after some vitamin B6-modulated partial metabolical degradation in the body, is excreted in the kidney, where it precipitates with calcium to form calcium oxalate kidney stones.”
Basically, this means that quinolones (and some other antibiotics) kill oxalobacter formigenes, a bacteria in the GI tract that is crucial for breaking down oxalates. When oxalates aren’t broken down properly in the GI tract, they move on to the kidneys where they form calcium oxalate kidney stones.
Kidney stones aren’t the only problems that oxalates cause though. Oxalates cause methylation problems that inhibit detoxification. According to Dr. Rostenberg’s article, OXALATES AND MTHFR: UNDERSTANDING THE GUT-KIDNEY AXIS:
“oxalates create biochemical problems that make methylation issues worse. Since oxalate problems cause sulfate problems, the genes most effected will be the SULT and other phase II related pathways. The sulfate molecule is key in order for the liver to perform the daily task of detoxification. If sulfate levels drop, then the body cannot use the SULT pathway to detoxify. Instead it will be forced to use other Phase II pathways which can put greater demand on pathways that are also genetically slowed down. When we consider other slowed Phase II detoxification gene SNPs such as NAT2, ALDH, COMT, GSH, GSS, UGT, and SOUX we can begin to see that a lack of sulfate molecules can have a broad negative impact on all of our detoxification pathways.”
Dr. Rostenberg goes on to say:
“As you will soon see, when oxalate levels are high, sulfate levels drop slowing down detoxification. Low sulfate levels put extra stress into the methylation cycle to provide the body with sulfate molecules. In individuals with an impaired methylation cycle this can provoke methylation issues such as high homocysteine, developmental disorders, gallbladder dysfunction, hormone imbalances, excess inflammation, poor growth and to name but a few. So with oxalate issues and the biochemical chaos it creates, a great deal of stress is placed on the methylation cycle.”
In OXALATES AND MTHFR: UNDERSTANDING THE GUT-KIDNEY AXIS Dr. Rostenberg asserts that a poorly functioning gallbladder is a cause of oxalate overload. While I agree that a well-functioning gallbladder and liver are necessary for all aspects of health, I wonder if the decimation of vital gut bacteria, like oxalobacter formigenes, by antibiotics like fluoroquinolones, is what starts oxalate toxicity damage.
Fluoroquinolone Destruction of Vital Gut Microbes
A floxie friend just noted that she got her microbiome mapped by ubiome and, “my Ubiome results tell me I have NO oxalobacter at all.” Additionally, her results showed that, “I also have NO bifidobacterium strains AT ALL.” (According to the wikipedia article for bifidobacterium, “Different species and/or strains of bifidobacteria may exert a range of beneficial health effects, including the regulation of intestinal microbial homeostasis, the inhibition of pathogens and harmful bacteria that colonize and/or infect the gut mucosa, the modulation of local and systemic immune responses, the repression of procarcinogenic enzymatic activities within the microbiota, the production of vitamins, and the bioconversion of a number of dietary compounds into bioactive molecules.”) Both oxalobacter and bifidobacerium are necessary for many aspects of health.
Might the root of fluoroquinolone toxicity, and possibly other chronic diseases of modernity, be the killing off vital microbes like oxalobacter and bifidobacerium?
The depletion of oxalobacter formigenes, and other microbes, doesn’t just affect the gut. As Dr. Rostenberg noted above, oxalate problems (caused by not breaking down oxalates in the gut – caused, in part, by killing oxalobacter formigenes with antibiotics) lead to sulfate problems, which leads to methylation problems, which leads to detoxification problems, which leads to heavy metal overload and toxicity. Additionally, “Sulfate helps us seal our leaky gut and strengthen our body’s bones, ligaments and tendons; and it is required for Phase II detoxification of all kinds of nasty toxins, hormones and heavy metals. In fact, sulfate is so important for our health that it is the 4th most common nutrient in our blood stream!” (source) Sulfate is also necessary for proper hormonal function, “When sulfate levels are low, the body won’t just have disturbed liver function, it will also suffer with all kinds of hormone problems.” (source) As anyone who has experienced hormonal dysfunction will attest, hormonal disorders affect every aspect of health. In “Fluoroquinolone Antibiotics and Thyroid Problems: Is there a Connection?” it is noted that fluoroquinolones are endocrine disruptors that lead to disruption of thyroid function, and additional information about the effects of fluoroquinolones on the thyroid can be found on http://fluoroquinolonethyroid.com/.
The most thoroughly documented and accepted consequence of oxalate overload is kidney-stones. Kidney-stones are incredibly painful, and they can cause damage to the kidneys. In addition to kidney-stones, it is noted in The Role of Oxalates in Autism and Chronic Disorders that, “Even though oxalate crystals are most common in the kidney, they also can form in virtually any other tissue in the body, including the brain and the blood-brain barrier. Oxalate crystals resembling pieces of glass can form in the heart muscle. As the heart muscle contracts, these pieces of oxalate crystals actually tear into the tissue. If these crystals are deposited in skeletal muscle, normal movement and exercise can be very painful. I’m convinced this is also one of the factors responsible for fibromyalgia. Oxalates may also cause thyroid disease as they react in thyroid tissue.”
In THE DOWN SIDE TO HIGH OXALATES – PROBLEMS WITH SULFATE, B6, GUT, AND METHYLATION, Dr. Rostenberg goes over the connections between oxalates, sulfate depletion (by oxalates), and liver problems, hormonal problems, GI problems including leaky gut, cancer, and autism. Additionally, it’s linked to high homocysteine which is linked to blood clots, strokes, and heart attacks.
Fluoroquinolones and Oxalates
There are literally twenty plausible theories as to how fluoroquinolones cause fluoroquinolone toxicity—a multi-symptom, often chronic, illness that is similar to autoimmune diseases, mysterious diseases like fibromyalgia and CFS/ME, endocrine disruption diseases, and more. Though much of the research into fluoroquinolone toxicity has focused on what fluoroquinolones do to cells (especially mitochondria), as information about the importance of the microbiome emerges, it becomes plausible (and even likely) that the destruction of important microbes by fluoroquinolones is a large contributor to fluoroquinolone toxicity.
In Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues Dr. Martin J. Blaser hypothesizes that the extinction of critical microbes is behind many of the diseases of modernity, from autoimmune diseases to obesity. Dr. Blaser focuses primarily on h. pylori and its connection with both preventing inflammation and causing ulcers, but he acknowledges that many other microbes play important roles in human health and well-being. I wonder if oxalobacter formigenes and other microbial communities are just as interesting, contradictory, and important as h. pylori. I suspect so, and I also suspect that the basic hypothesis that missing microbes (from antibiotic use, glyphosate, and the Western diet) are causing the many diseases of modernity, is, indeed, true.
Fluoroquinolones obliterate the gut, and kill both helpful and harmful bacteria. In wiping out essential species of bacteria in our gut, are they starting the cycle of inflammation and chronic disease in genetically susceptible individuals? It certainly sounds like a reasonably hypothesis to me.
Can the gut be healed?
Can species of bacteria that have been depleted by fluoroquinolone antibiotics be replenished? Do probiotic supplements help? Can changing one’s diet help? What about fecal transplants?
Those are all million dollar questions that many researchers are working on answering. Unfortunately, I don’t know the answers to them. I am certainly hopeful that the gut can be healed, and I know from personal experience that healing after fluoroquinolone antibiotic toxicity can occur. Organizations like The Human Microbiome Project and Ubiome have many smart and capable scientists who are working to answer those questions, and more.
Until those questions can be more thoroughly answered, here are some helpful resources:
Resources for Healing
Trying Low Oxalates Facebook Group – https://www.facebook.com/groups/TryingLowOxalates/
Information about a low-oxalate diet can be found on Low Oxalate Info: Hope and Healing on the Low Oxalate Diet.
Dr. Rostenberg’s protocol for reducing oxalates can also be found here – http://www.beyondmthfr.com/high-oxalates/. Additional information from Dr. Rostenberg can be found through the Contact page on http://www.beyondmthfr.com/.
Additional information about MTHFR and other gene mutations, and how they affect health, can be found on https://mthfrsupport.com/.
Dr. Rostenberg’s videos on oxalates: