The Lumina Probiotic May Cause Blindness in the Same Way as Methanol

I think we may have hit Scott Alexander's <1% scenario.

For the past several months I have been slowly losing my vision, and I may be able to trace it back to taking the Lumina Probiotic. Or rather, one of its byproducts that isn’t listed in the advertising.

For some background, I received my BCS3-L1 about three months back. I donated the bulk to my partner who is prone to cavities, but after administration I changed my mind and decided to inoculate myself using the residue left in the vial. Over the next several months I noticed transient dimming of vision, eye discomfort, like a sort of pressure behind the globes that would come and go, an increase in flickering stars every so often and an increase in eye floaters, all of which I ascribed to my kratom habit (I always take it with some lemonade, hint hint). Slowly this began to worsen, the darkness pursued me even during the day at work though I only took one small dose of kratom per day, in the evening.

I began to have headaches, a dull pain directly behind both eyes when I would drink my (full sugar) tea, and then even after meals. I did not realize the relevance of this at first. Then things got bad. I noticed fading of colors, especially red, and a decline in visual contrast as the whole world began to disappear into grey mist. It was when I realized my vision was significantly duller in my right eye that I truly began to worry. That means it cannot be perceptual, since the optic chiasm splits the nerve fibers into left and right fields across both eyes. Colors indeed were different between the two at this point. Reds were pink in the left eye, orange tinted in the right. Greens not quite as bad, but slightly yellowed. Blue still okay. I quit kratom entirely, yet things did not improve. This was about a month ago, and my vision has continued to dim in both eyes. At this point it is as if I live at the bottom of the ocean, everything has a strange greyish blue cast to it and I can hardly see any contrast anymore. Though my acuity is still mostly holding up.

Diagnosis?

My symptoms combined with testing are highly sensitive and specific for a few types of optic neuropathy, damage to the optic nerve which is usually permanent since we have no way of regrowing those axons. Imaging showed no damage to the retina or the optic disk a few weeks back meaning it’s confined to the retrobulbar zone or more likely is still subclinical. OCT scan showed mild thickening across my right eye, the worse one, but the nerve fiber layer appeared okay (said my ophthalmologist.) Visual fields were normal when they checked, though things are worse now. MRI was clear, no masses or lesions visualized, just in case you were thinking tumor or demyelinating disease. All of this taken together suggests toxic or nutritional optic neuropathy. Fading colors, dimming lights, with a slow progressive onset combined with minimal clinical findings in the retina is fairly conclusive. Nutritional causes have been excluded by blood tests, leaving just toxic optic neuropathy.

The Toxin?

My contention: formate. Produced by the BCS3-L1 bacteria living in my mouth. No other exposure can be identified and the course lines up just too well.

Let me explain.

The Lumina Probiotic aka BCS3-L1 is a genetically modified strain of Streptococcus Mutans that was originally billed as producing ethanol and acetoin instead of lactic acid, outcompeting the wild type upon inoculation and thus dramatically reducing incidence of caries caused by acid buildup on the teeth. It lacks lactate dehydrogenase, so it is forced to rely upon mixed acid fermentation for all its metabolism. Wild type S. Mutans is known to rely on this pathway when sufficient glucose is not present in media, but it quickly switches to lactic acid fermentation when sufficient sugar is present. Lactic acid fermentation produces lactate, mixed acid fermentation produces ethanol and acetoin yeah yeah, we all know that. But wait. That’s not true. BCS3-L1’s alternative metabolic pathway doesn’t just produce ethanol. It actually produces four times as much formate as well.

So what’s the issue with formate? Well, it’s the end metabolic byproduct that causes blindness in methanol poisoning. It is a known mitochondrial toxin that mainly affects the retina and optic nerve. It inhibits cytochrome oxidase essentially causing hypoxic damage within photoreceptors and retinal ganglion cells preferentially, as they are extremely metabolically active. Formate is already produced within the oral microbiome, but usually not in large amounts in response to sugar intake. At least not that I can find. It is produced by E. Coli in the gut as well, but that’s much further away from your eyes.

So how much formate are we talking about here? Considering Lao Mein’s article and the ratios in the original BCS3-L1 paper, it must be on the order of at least a few percent in saliva, and that’s not counting direct mucosal exposure. Is that enough to damage the retina and optic nerves when absorbed through tissue a few millimeters away? I really just don’t know. When talking about methanol, which is entirely metabolized to formic acid, a few milliliters is enough to cause permanent blindness. Nobody regularly drinks dilute formate solution and they definitely don’t smear it on their gums. Oh yeah, I guess I didn’t mention the jaw pain I was having before this started as well. Interesting, right? And in case you were wondering, this wouldn’t have shown up in the original BCS3-L1 rodent toxicity studies either as most non-primate animals metabolize formate much more efficiently, including rats. This has led to difficulties creating a rodent model of methanol toxicity, in fact.

My Fate?

If this is what’s happening to me, my situation does not look good. Chronic methanol exposure is not common and not well studied, and chronic formate exposure basically doesn’t happen, but it sounds like it might be visual darkening for a few months and then lights out forever. Upon hatching this theory of mine I tried systemic clindamycin for a few days which actually dramatically worsened my vision, little did I realize antibiotics are about the worst thing you can take when your eyes are metabolically compromised. Mitochondria are basically just bacteria, after all. I’m currently using chlorhexidine mouthwash several times a day and desperately trying to avoid sugar while I wait for my referral to neuro-ophthalmology. I’m not sure if any intervention will save me at this point, short of maybe pulling out all of my teeth. I don’t know if I can bring myself to do that, especially when I might be wrong. I’m basically just hoping that one report of the bacteria being eliminated with chlorhexidine is reproducible. I’m going to get my teeth professionally cleaned as well. At best it seems that I’ll likely never see a bright light or vibrant color ever again for the rest of my life, unless we get an aligned AGI that can fix me (<1%) or we start funding the NIH again and the scientists actually come back (0%).

And what might become of the others if what I say is correct? Maybe my eyes are more sensitive to metabolic disturbances than most. I have checked my 23andme raw data for Leber’s hereditary optic neuropathy variants and two of the three main variants they check came up negative, but who knows. It could also be that I have less functional reserve than most. Vision damage is usually not appreciated until 25-50% of retinal ganglion cells are disabled. Maybe the rest of the Lumina victims are still on the way, years down the line.

I sure hope I’m wrong though. I mean it, somebody please prove me wrong because this sucks if true. I am not any sort of molecular biologist whatsoever, I’m just pointing out a strange omission in all the Lumina discussion and an eerie correspondence with these symptoms of mine. Either way I think I’m probably cooked. I don’t know if I’m the kind of person who can just bounce back from permanent blindness, but I guess I’m going to find out.