Prostaglandin and COX-2: ME/CFS, Ulcerative Colitis and Gut Permeability

When I developed ulcerative colitis, I had been on several months of treatment as prescribed by Prof Kenny De Meirleir, an myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) researcher and clinician. The treatment included antibiotics to treat a suspected chronic Bartonella infection. I also took a bunch of supplements and injections as part of his protocol.

Prior to treatment I had undergone a barrage of immune system tests, including prostaglandin E2 (PGE2) and interleukin 8 (IL-8) both of which were highly elevated, especially PGE2. I had loads of other markers involved with inflammation that were very high. Over the course of treatment, the others reduced, while PGE2 and IL-8 did not. They went up even further.

One of the supplements I was on was berberine, which has a bunch of effects on the gutflora, which aren’t necessarily all good though it’s often touted as a cure-all (but that’s a whole other topic). Something else that Berberine does is reduce PGE2 synthesis (several studies showing that).

Well it didn’t work for me. Here are my results:

Prostaglandin E2 (normal, 0.17-6.4)
Jan 2013 (prior to any treatment): 28.3
August 2013 (after a few months on treatment): 68.95
Dec 2014 (after eight/nine months of treatment): 37.68

Prior to treatment, and before I developed ulcerative colitis (UC), I had significantly elevated PGE2. I am unaware of anyone measuring PGE2 in ME/CFS patients and reporting it as a finding, though I know others who have been tested and have elevated PGE2 and Maes et al. have reported elevated cyclo-oxygenase-2 (COX-2) in ME/CFS patients (which leads to production of PGE2 – more on that in a minute).

Although the cause of UC is also unknown, several pathogenic bacteria have been put forward as culprits, and some are known to induce the expression on PGE2 during mucosal bacterial infection. (Mallory Agard et al.). I developed UC in September 2013 as a direct result of the antibiotics I was taking which significantly disrupted my gut flora. In November I started taking Pentasa (mesalazine). Although the Dec 2013 result was still very high (higher than pre-treatment, in fact) it did drop between August and Dec 2014. Did the mesalazine cause that drop?

COX enxymes (also known as prostaglandin-endoperoxide synthase) catalyze the conversion of arachidonic acid into prostaglandins, including PGE2. Mesalazine has been shown to down regulate the COX-2/PGE2 axis in inflammatory cells in the colonic mucosa of UC patients (Collier HO et al. and Sharon P et al.) So, mesalazine seems to reduce PGE2 via COX-2 inhibition.

Even now, with my UC much better, if I forget a dose of mesalazine I can feel my bodies inflammation ramp right up and it stays that way until I take the mesalazine and it gets to work (slow release, so often this is up to a day). So maybe this is relevant to some people with ME/CFS, not just UC.

And although I’m not going to focus on it in this blog post, it’s interesting to note that activated B-cells highly express COX-2, and that inhibition of COX-2 dramatically reduces B-cell antibody production (Elizabeth P. Ryan et al). Could this be part of why Rituximab shows such great promise in the treatment of ME/CFS (Fluge Ø et al.) and is now in phase III trials?

Prostaglandin Receptors and Gut Permeability

PGE2 is produced by a bunch of tissues including those of the gastrointestinal tract and it interacts with the epithelial cells via specific cell receptors, namely, EP1, EP2, EP3, EP4, each resulting in different biological consequences. So it is not PGE2 alone that determines the biological effect, the receptor type matters. When the colonic mucosa is inflamed, the EP2 receptor on cells are over-expressed (V. Takafuji et al.) and mucosal PGE2 release appears to increase in correlation with disease activity in UC (DS Rampton et al.).

A new study published in PLoS One by Lejeune M et al. suggests that these prostaglandin cell receptors are involved in gut permeability, with the epithelial layer being more permeable — as measured by transepithelial electrical resistance (TER) — in cells that express less EP2 receptors, resulting in a significant loss of the tight junction protein claudin-4 through proteosomal degradation. The study authors managed to show that it was the receptor that was responsible, not prostaglandin itself (as suggested previously by Rodríguez-Lagunas MJ et al.). Now let me dumb that down for when I’m reading this back to myself in a few day’s time: Loss of EP2 receptors on the colonic epithelium can decrease barrier integrity by degrading a particular protein responsible for tight junctions. But it’s the prostaglandin receptor which is important, not the prostaglandin.

PGE2 is also known to induce IL-8 through its affinity for the EP4 receptor (I Dey et al.). That may explain why my IL-8 also remained high while the others did not, and further demonstrates why PGE2 may be important.

The problem is that PGE2 has all kinds of impacts through these four cell receptor types that it interacts with. We are understanding better what these receptors do thanks in no small part to studies using knock down mice (for which we can thank Nobel Prize winner Mario Capecchi who introduced the concept. Wonderfully, he is now involved in the End ME/CFS Project) but there is still a lot we do not know.

There is some evidence that PGE2 is protective of the intestinal mucosa (Morteau O et al.) but remember, some pathogens are known to induce it’s production, so it clearly isn’t all good. But we’re getting a bit of a mixed message here. PGE2 is also ultimately responsible for inducing fever by acting on the hypothalamus which controls the bodies temperature setting. I don’t get fevers (people with ME/CFS usually don’t get colds/flu when exposed, for some unknown reason) so there must be more to it than just having high PGE2, else my high PGE2 would induce a constantly high temperature… I haven’t looked but I’m guessing this might have something to do with those different cell receptor subtypes again. Maybe a reader knows, and can enlighten me.

But let’s say our COX-2/PGE2 is high when it shouldn’t be (perhaps in ME/CFS and perhaps in IBD when we are in remission) then it may be a reasonable step to try and reduce it. If we wanted to try that then as well as mesalazine, a common but related drug, aspirin, is known to significantly inhibit COX activity, as do other NSAIDs (that’s how they work to reduce pain/inflammation). Generally, nonsteroidal anti-inflammatory drugs are sometimes considered a risk for IBD, both UC and Crohn’s because they are hard on the gut. Though aspirin seems not to have this negative impact in UC (Chan SS et al.)

A number of COX2 inhibitors came on the market and resulted in increased heart attacks and strokes, leading some to be withdrawn, and warnings to be added to traditional NSAIDs. COX2 is actually pretty essential, so drugs that inhibit it can be dangerous.

Mesalazine is generally considered to be very safe though – it’s the front-end treatment for ulcerative colitis and is taken long-term – why is that? I suspect it is because it acts at a very local level; the majority is not absorbed so it stays in the intestines (making it a great drug for treating inflammatory bowel diseases) without having too much systemic impact.

I guess what I’d really like to know is why PGE2 is elevated in UC in the first place (as we’ve known for a long time – Wiercinska-Drapalo A et al.) and seemingly also in some patients with ME/CFS (who commonly suffer gut dysfunctions, including leaky gut). Herpes viruses induce COX-2 (Kaul R et al.) so could it be that herpes viruses, long proposed as the pathogenesis of ME/CFS, are to blame? Who knows.

Speculation aside, I think if we want to reduce COX-2/PGE2 then our aim should not be to potently inhibit it but to lessen it if it is inappropriately high.

Let us take a look at what probiotics might do for us then. This study (Jan-Michel Otte et al.) showed that the probiotics VSL#3 and Mutaflor (E. coli Nissle 1917) “ameliorated induced COX-2 and PGE2 secretion.” That’s nice and might explain why these probiotics have proven helpful in IBD.

The study continues, “Lactobacillus acidophus, however, significantly increased COX-2 expression and PGE2 secretion.” So you want to avoid L. acidophus – something I already do, as it may reduce commensal E.coli. It’s hard to avoid entirely though as it is in many products, including VSL#3 which in this study, on balance, still reduced COX-2 and PGE2 through the other types of bacteria in the product.

Another study (R. Korhonen et al.) suggests that Lactobacillus rhamnosus GG induces COX-2. Maybe best to avoid that one too then. And yes, there are lots of foods and supplements out there which are known to reduce COX-2/PGE2 but that’s a whole other topic. But I can’t resist pointing you to one interesting study comparing the effects of Omega-3 and Omega-6 fatty acids (DiNicolantonio JJ et al.) on Cox-2/PGE2.

Which Genera of Bacteria are Covered by Probiotics, and Which Aren’t?

Probiotics: more holes than whole.

Probiotics: more holes than whole.

There are many brands of probiotics available, but the reality is that only a slim piece of the broad spectrum of commensal bacteria are available to buy as probiotic supplements. Different brands – but most are focused on the same types of bacteria.

So which friendly bacteria are actually available? And which aren’t?

It will take far less time for me to tell you what is available, than what isn’t!

Only a few genera of bacteria are available as probiotics, and although within this limited range there are many different species and strains sold by different brands, as most of the data we can actually get on what is present in our own gut is based on 16S rRNA testing (which predominantly tells you Genus level data), I figure that a list at the genus level is where we should start looking. Yes, different species and different strains do matter, but if we can’t get any species or any strain for a particular genera that we are lacking in, then that’s the real limiter.

So I’m starting with a list of which genera are covered by commercially available probiotics. I’ll be updating this list as more probiotics appear on the market. If you see something that is missing then please let me know! In time, I’ll maybe go and add species and strain level data.

For genera that are covered by many brands, I’m not listing the options because you can’t find them easily via a search engine or in a health store, but I’ve added links to the more tricky to find ones (but I haven’t tried any of them myself, so it’s not a recommendation).

Stuff not covered by the list:
Bacteria that you can buy but which are not listed as probiotics for consumption – for instance, starter kits for foods and beverages, or for veterinary use, or for research purposes – I am not listing these. I am also not listing any yeasts, just bacteria, and also absent are soil based bacteria that are not commonly found to colonize the human gut.

Above each genus is a heading stating which Phylum, Class, and Order it belongs to.

Firmicutes > Bacilli > Lactobacillales
These are the bacteria commonly referred to as lactic acid bacteria (LAB). There are several different genera from different families of bacteria grouped together as LABs and these make up the vast majority of probiotic supplements on the market. Many can be gained naturally by eating various non-pasteurized fermented foods.

Lactobacillus
Streptococcus
Lactococcus
Leuconostoc
Pedicoccus (NutriLots)
Enterococcus (Dr. Ohhira’s Formula OR Symprove OR Bifilac OR Threelac OR BIO-THREE)
Oenococcus (as the name suggests, this bacteria is involved in wine making and several sites sell this for wine production, though not strictly as a probiotic supplement)
Weisella (Oral Diet)

Actinobacteria > Bifidobacteriales > Bifidobacteriaceae

As with the lactobacillales above, these Bifidobacterium are sometimes referred to as lactic acid bacteria (LAB) and can be found in many fermented foods as well as being commonly produced as a probiotic supplement. However, they actually belong to a different phylum of bacteria than the Lactobacillales above.

Bifidobacterium

Firmicutes > Bacilli > Bacillales >
Bacillus (Prescript Assist OR Microflora OR Bifilac OR Threelac OR BIO-THREE)
Staphylococcus (not available as a supplement but you can get it from Dawadawa – fermented locust beans)

Firmicutes > Clostridia > Clostridiales
Clostridium (Bifilac OR AOR Probiotic-3 OR BIO-THREE OR Miyarisan which you can buy outside of Japan on ebay)

Proteobacteria > Gammaproteobacteria > Enterobacteriales
Escherichia (Mutaflor)

Proteobacteria > Beta Protecobacteria > Burkholderiales
Alcaligenes (not available as a supplement but you can get it from Gari – fermented cassava)

Actinobacteria > Actinobacteria > Actinomycetales
Corynebacterium (not available as a supplement but you can get it from Gari – fermented cassava, or Ogi – fermented maize)
Propionibacterium (not available as a supplement but you can get it from Swiss type cheese such as Emmental cheese, Gruyere, and Leerdammer)

That’s it folks – I hope you weren’t expecting a big list!
If like me, you were hoping for some other Clostridiales such as Roseburia, Coprococcus or Ruminococcus, or anything from the Bacteroidetes phylum, then I’m sorry to disappoint you will this list. It’s clear to see why some people turn to faecal transplants as an answer. We’ll talk about that further down the line.

The Science of Sauerkraut

Sauerkraut-wikipediaFermented foods are often promoted as a good way to get beneficial bacteria into your digestive tract if you have bowel problems like ulcerative colitis, Crohn’s disease or IBS, or one of the many other conditions that come bundled with free bowel dysfunction, such as ME/CFS. And it’s true; gross-tasting fermented food can provide you with much needed friendly bacteria. But it is not a panacea.

The reality is that only certain bacteria are produced in the making of sauerkraut and other fermented foods. If you already have these in your gut and are lacking something else, then sauerkraut isn’t going to fix your problems. You might have endured eating it for no good reason!

So it might be worth a go, but if you want to be really scientific about it then you can first find out what bacteria are in your gut with a test through a company like uBiome or AmericanGut and compare your results to see whether the types of bacteria present in sauerkraut are already present in your gut, or not. You may find there is no need and thus avoid the misery of eating this rank ‘food’.

How does the fermentation process work?
There are a bunch of factors that influence which bacteria are in your sauerkraut, pH, length of fermentation, temperature, salinity, etc. and there is a large turnover of different types of bacteria as the fermentation progresses with the dominant species changing as the fermentation environment becomes more acidic.

What happens is that lactic acid bacteria (LABs) metabolise the glucose and fructose within the cabbage and produce lactic acid, and to a lesser degree acetic acid and mannitol, as by-products. Lactic acid overtakes glucose in concentration after just 7 days of fermentation. As the environment changes, so do the species of bacteria that are more suited to the conditions present.

As the name suggests, LABs are a group of related bacteria that all produce lactic acid, and the production of this acid helps to inhibits pathogenic bacteria and other organisms that might cause spoilage. LABs are generally considered to be safe, and occur in many foods such as cheese, beer and wine. They are present in healthy guts and often absent in autoimmune conditions. They belong to the Order Lactobacillales and if I look at my uBiome results, it seems that mine are much lower than average:

Lactobacillales

And this is not explained by my having been on long-term antibiotics. Many Lactobacillales are antibiotic resistant [2] and looking at my result compared to the antibiotic comparison group, the normal range is actually a lot higher than other groups, as high as 14.3% (because other types of bacteria are killed while Lactobacillales survived) which is double that of healthy omnivores. Mine are probably low for some other reason; either because of disease, or due to some other unknown factor. Increasing my lacrobacillales is unlikely to cure me of anything, but it may help a bit.

Exactly which bacteria are in the sauerkraut?
There are some limitations to the studies that have tried to answer this question. As fermentation progresses and the environment becomes more acidic, some bacteria that are present at the start of the process may be dead by the end. Some test methods would identify both the living and dead types without being able to say which ones were alive at the end. Other test methods get around this by culturing living bacteria though this also has limitations as some types of bacteria do not culture well.

That said, A 2007 study by Plengvidhya et al [1] looked at cultured isolates and also 16S rRNA gene sequence analysis in commercial samples and reported a rapid increase in the numbers of LABs and a rapid decrease in populations of Enterobacteriaceae in the first week of fermentation.

They conclude that “Under normal conditions, the fermentation is essentially complete within 2 weeks, with the most-acid-tolerant species, Lactobacillus. plantarum, predominating.”

L. plantarum was by far the dominant species, making up between 80% and 100% of the population after 14 days in different samples. Sadly, a small population of bacteria, less than 10%, was classified as “Unknown” at 14 days, followed by relatively small populations of Lactobacillus. brevis and Lactobacillus. paraplantarum.

Before this, at 7 and 9 days you also see these other LABs present that do not survive to 14 days:
Leuconostoc argentinum, Lactobacillus curvatus, Lactobacillus coryniformis, Leuconostoc fallax, Pediococcus pentosaceus. I suppose, if you felt that having these present in your gut were a good thing, then you could consume your sauerkraut at this earlier point.

Leuconostoc mesenteroides, Weissella species and Leuconostoc citreum are present earlier in the process in the first few days and are key for kicking off the fermentation process.

How much bacteria is present? I could just take some pills which taste a lot nicer…
It varies over the course of the fermentation but we are talking about billions of colony forming units per gram. L. plantarum and L. brevis have been well studied and have shown a wide variety of health benefits. You can buy some of the above as pro-biotics, if you prefer.

Fine, I want some of this nasty stuff. How do I make it?

fermenting crock pot

fermenting crock pot

Commercially it is made in big tanks, or in wooden barrels, and you can buy some and save yourself all the effort if you like. Just make sure you buy unpasteurized sauerkraut, or else it’s just sauerkraut with dead bacteria, and unless you like the way it tastes (hardly likely) then there’s little point eating it.

At home, it is typically made one of two ways: in a fermenting crock, or in a sealed jar. In either case, one of the main things you’re trying to do is remove all the oxygen from the equation. Lactic acid bacteria do not need it and many pathogenic bacteria do. I have not tried making it in a jar yet; it appears to be a bit hit and miss while using a fermenting crock makes it easy to keep the oxygen out. If you are going to try it in a jar then use a one way valve – this will allow any oxygen out but not let new oxygen back in.

How do fermenting crocks work?
It is just a container with a special top with a moat in it that you poor water in, and the lid sits in this moat, meaning that air cannot get in. Air from inside (the original air and the gasses produced by the bacteria) are allowed to escape via a couple of small nooks in the lid; they work to let air out but not in.

The other thing it comes with are some weights, usually ceramic which help to hold the cabbage under the salt water. This again helps to keep things anaerobic.

You don’t need a starter or anything like that, the bacteria naturally on the cabbage itself are what will multiply in the fermenting process. The only ingredients are cabbage (obviously), water and salt. Last time I used a standard cabbage, this time it is an organic one. I think either should work fine.

So, fermenting with a crock. They can be quite expensive. I bought mine, a second-hand 5 litre one made by Gairtpf for £20 on ebay. It was open but never actually used. They are heavy so you can get them for a bargain if you are local to the seller.

Things you’ll need
Cabbage (go figure)
Any other veg if you want, such as carrot or onion. I plan on trying this next time.
Salt
Water (I use natural mineral water but tap water would be okay)

First, before you begin, make sure everything is really clean, but also rinsed well to ensure there are no antibacterial agents left about, especially inside the container, as they may interfere with what we’re trying to do here.

My cabbage weighed 1.6lb. I used two cabbages last time, which turned into three or four large jars at the end of the process. But I didn’t eat it all (did I mention that I don’t like this stuff because it tastes like sour cabbage?….oh). Take two big outer leaves off the cabbage and set them aside. Shred the rest of the cabbage. It doesn’t matter how finely.

sauerkraut2Once you have shredded the cabbage, you add it to the crock in layers with the salt. Once it is all added you are supposed to pound the cabbage to get it to release its liquid from inside. You need approximately one tablespoon of salt per 1.5lb of cabbage. I did this but because I have ME/CFS I have little strength, so I just do a little and it seems to work fine even though it is not well pounded. The salt pulls water out of the cabbage, through osmosis. 24 hours later (or right away if you get knackered like I did and just want the ordeal to be over) you add the two leaves that you set aside, on top (this helps to keep the shredded cabbage from floating to the top) you place the weights on top of everything and then add enough water to just cover the cabbage and the weights.

Now you cover the Fermentation crock and fill the moat with water. Remember to check the moat daily as the water will evaporate and you will need to top it up. If you are making it in a jar then put the lid on it. Place it somewhere coolish (ideally, 18 degrees C, but room temperature is fine).

How do you know when it is done?
pH. It generally takes 2-4 weeks and as discussed above, the bacteria in the pot changes over time. So you will get different bacteria depending on when you decide to tuck in, and perhaps this will influence when you consider yours ready.

Last time I made sauerkraut it took 3 weeks. I tested the pH at two weeks and that told me it wasn’t ready (though it would have been safe to eat). After three weeks I was down around 3.6 which is where you want to be if you want completely cured sauerkraut. So get yourself some litmus paper.

Once it’s ready it keeps really well. You put it in a jar with a lid and cover it in the brine. It does not have to be refrigerated but it is a good idea and will extend its shelf life. You do, perhaps, start to get used to it once you eat it, and I suspect that if you grew up eating it, rather than say custard doughnuts, chocolate or pretzels, then you may even have convinced yourself that you like it. Personally, I think the bacteria ate the good bit and left me the pungent nastiness that is sauerkraut because they hate me. But I’m still gonna eat it, not for my sake, but for my gut’s.

If you want to help people like me who suffer from ME/CFS who have waited a long time for world class research into our gut microbiome, then please check out the Microbe Discovery Project and consider helping out.


sources:
1. Plengvidhya V et al. Appl Environ Microbiol. Dec 2007. DNA Fingerprinting of Lactic Acid Bacteria in Sauerkraut Fermentations
2. Zhou N et al. J Dairy Sci. Sep 2012. Antibiotic resistance of lactic acid bacteria isolated from Chinese yogurts
Image credit: sauerkraut in jar – wikipedia commons.

uBiome making good on their word: more of my gut flora have been ID’d

Eggerthella: one of the newly identified residents of my gut

Eggerthella: one of the newly identified residents of my gut

True to their word, uBiome have been making good on their promise to further improve their algorithms which identify and assign your gut bacteria to their taxonomic ranks. Several weeks ago I wrote about the missing portion of data in my uBiome results, which was particularly stark at the genus level. Back then, only 73.68% of my genus level bacteria were classified. uBiome told me they were continually adding to their database of microbes and improving the algorithms that identify them. Now, 80.284% has been assigned. So we’re getting there at an okay rate. We’ve gone from a quarter missing down to a fifth. Good job uBiome.

In most cases this is due to completely new genera of bacteria being identified; here are all the new ones that presumably will show up on everyone’s reports, provided any are present in your gut (family name in parentheses):

  • Eggerthella (Coriobacteriaceae)
  • Flavonifactor (unclassified Clostridiales)
  • Erysipelatoclostridium (Erysipelotrichaeceae)
  • Turibacter (Erysipelotrichaeceae)
  • Dielma (Erysipelotrichaeceae)
  • Dialister (Veillonellaceae)
  • Veillonella (Veillonellaceae)
  • Megasphaera (Veillonellaceae)
  • Bilophila (Desulfovibrionaceae)
  • Actinobacillus (Pasteurellaceae)

There are a couple of other very minor changes that are a refinement of decimal places, with some going from 0.01 down to 0.00400 and some others going up, e.g. from 27.9 to 28.0. I expect there may be some additional movements like these going forward.

So where does this leave me?
All of the new ones above are normal, or high in number. Erysipelatoclostridium for instance, is more than 9 times the highest end of normal (healthy omnivores). Although I may need to address these, I’m not going to focus on them in this post. My first effort to fix my gut is to nurture the things that are low, then I’ll deal with anything left which remains too high. I’ll probably write about which of my gut passengers might be pathogens at a later date, but for now I’m focused on what’s low.

I previously did some analysis of my gut results following antibiotics, and have now taken a closer look, including all this new data. Things are still subject to change because that missing 20% should appear at some point and genera that are currently low might suddenly climb as a result. But taking the data as it is at the moment, these are the things that I am very low in, and which the antibiotics obviously beat the crap out of:

The Low List
– Roseburia (0.147%)
– Coprococcus (0.113%)
– Pseudobutyrivibrio (0.0764%)
– Streptococcus (0.0664%)
– Ruminococcus (0.0161%)
– Anaeroplasma (0.0121%)
– Butyrivibrio (0.0121%)
– Rhodanobacter (0.00400%)
– Phascolarctobacterium (0.00400%)

– Anaerococcus (0.00400%)
– Subdoligranulum (0.00400%)

Eubacterium is also low (0.179%) but nowhere near as bad as those listed above. My guess is that Eubacterium will recover without much tailored effort on my part. Some of the others are going to be much harder to restore to normal levels and may need specific intervention.

My biggest concerns are Roseburia, Ruminococcus, Rhodanobacter, and Coprococcus; these are not only very low compared to the average norm but are also well outside the normal ranges too.

Rumnococcus

Roseburia

Rhodanobacter

Coprococcus

For the others that are low, the normal range (in green) includes values as low as zero, suggesting that my very low values could be considered normal, even if well below average. Here is such an example:

Streptococcus

I’d imagine that many or most of these are in fact not normal but represent the reality that many of us are routinely on antibiotics on a regular basis and have poor diet; I’ll be much happier if these move closer to the normal average.

I am sure biffidobacterium would have been present on the low list were it not for my taking a biffidobacterium containing pro-biotic all the while I was on antibiotics. The same pro-biotic tablet (Vitafytea bififlor forte) only contained one biffido species so I still feel I need to diversify there and am now taking a potent five strain powder. The pro-biotic tablet I had been taking also contained Lactobacillus rhamnosus and Lactobacillus acidophilus. L.Acidophilus is something I want to avoid now because of its negative impact on E.coli, many strains of which are good to have. But I should have some Lactobacillus in my results but they are not showing up – my bet is that they are in that missing 20% at the moment *sigh*. Can’t uBiome order some common pro-biotics, sequence them and then add them to their database? Wouldn’t that be easy? Well until Lactobaccillus shows up, I can only guess and I may well start taking a multi-strain Lactobacillus powder.

Bifidobacterium and Lactobacillus aside, most of the bacteria I am low in are not available in a pro-biotic supplement. Many have not even been well researched, meaning it is difficult to decide what pre-biotics and diet modifications you can make to nurture them. Animalpharm has a load of good information, including this page on Roseburia, so that’s something I’m digesting at the moment, but I’ll need ideas for the others too.

So this is a plea to readers: if you know anything about how to nurture these small numbers of survivors on my ‘Low List’ then please send me a message, tweet me, or leave a comment at the bottom. Thanks.

uBiome are also improving their visualization tools. They’re still not fully-baked yet, but I like the way they’re going with it. Lots of power to compare between your own results, including different types of tests (nose, skin, mouth, gut, genitals) and with other groups of people (different diets, drinkers, weight changes, antibiotics), and they appear to be giving some kind of indicator of sample sizes in these comparison groups too, which is important.

New links to relevant external content have appeared as well as a ‘community content’ heading – nothing in this last one yet, but I look forward to what might appear here in the future.

The one thing missing is disease groups. I know that uBiome will have already ruled this out as they don’t want to fall out with the FDA as 23andme have. But perhaps they could allow users to create their own tags to their samples and for those tags to be optionally public and searchable when others are adding tags to their own samples. This would allow people to make comparisons independent of uBiome specific labelling, and would also allow more unusual sample types to be compared more easily; for instance, the lovely Dr Grace suggested via Twitter that I might want to test the soil in my garden where my home-grown organic veg grows. I think that’s a fantastic idea because my main motivation for growing the veg in the first place is to expose myself to friendly soil organisms that I might lack. It would be handy to know for sure what exactly is in there and up for grabs!

If you’re interested in finding out what’s in your own gut, so you can start charging rent or hand the nasties an eviction notice then you can get a kit from uBiome’s website; but before you do, please check out and consider making a donation to the Microbe Discovery Project – the millions of people with ME/CFS have waited a long long time for a top scientist to take an interest and now they have the ‘Virus Hunter’ Ian Lipkin, but without any government funding, they need your help to fund this world class study of the gut.

Thanks, I appreciate it.

DjangoOh, and those share and follow buttons you’re looking for…those are below if you’re on a smartphone or at the top of the page if you’re on a computer…over on the right hand side…no, your other right. That’s it, you got it.

Image credit: Complete genome sequence of Eggerthella lenta type strain, Standards in Genomic Sciences

I Like My Colon Just Fine Where It Is, Thanks: A Tale of Fibre and Starch

I was started on medication the very same day I was diagnosed with ulcerative colitis.

PENTASA

Hard to swallow

Mesalazine comes in different forms, but the one I was prescribed was made for a giant; quite possibly it is the largest tablet ever made. I took four a day. They made no difference.

Then two rounds of prednisolone made no difference either. I explained in my previous post, how antibiotics triggered my ulcerative colitis and how stopping them helped me get better. But before that I had to sort out my diet and was referred to a dietician for help.

I was a 6 or 7 on the Bristol Stool Guide (named after the city where I was born) and I had lost 45lb, leaving my excellent gastroenterologist so concerned about the rapid and continuing weight loss, that she booked me in for a full body CT scan in case I also had a cancer tumour somewhere too. If that was normal then I was going to move onto the harder drugs – Azathioprine (Imuran) and Infliximab. If they failed then I might have needed surgery to remove my colon. It was fibre and starch that helped me avoid these eventualities.

“Stay away from fibre,” the dietician said.

“Oh, Really?”

“Yes.”

“Why?” I asked.

“It creates a lot of gas which patients find painful and increases bowel movements, and we’re trying to reduce your bowel movements. A lot of people find the specific carbohydrate diet (SCD) beneficial.”

I wasn’t convinced. I don’t doubt that some people with UC find the SCD helpful – I agree with some of it – but my gut had been giving me it’s own opinion, and I had begun excluding a whole load of stuff based on what it said. A pattern was emerging and the pattern was that gluten, maize, egg, most dairy, tea, coffee, and additives were bad; and that fibre, starch and meat were good. My gut spoke to me in a voice like Audrey out of Little Shop of Horrors –  it screamed, “Feed me Clark. Feed me. Must be starch. Must be fibre. MORE! MORE!”

I think dieticians sometimes assume fibre is the baddie because in healthy people it makes up the majority of waste that comes out the other end. But when you have UC everything comes out the other end – fast. This isn’t fibre’s fault though. There is no time for your body to absorb what it can and leave only the fibre behind. The problem is not the fibre. The problem is an immune reaction, and certain foods seem to precipitate this reaction.

Breakfast is oat porridge, made with oat milk which is really just ground oats and water. Every. Single. Monotonous. Day.

Sweet Potato

Here are some sweet potatoes my wife dug up today

I get more variety in my lunch and dinner though, which consist of vegetables, fruit, rice and meat. I get through so many potatoes that I started growing them myself. And I take potato starch as a supplement too. And this is where I struggle with the SCD, because potatoes, and their starch is strictly illegal. It’s also interesting that some versions of the SCD allow soaked legumes, which contain starch, but these are another thing that my gut says no to.

When I finally figured out the last few things to cut out so that my gut didn’t complain any more (soya lecithin was last), my colon finally got a break and started to heal up. I eat stuff that would be considered illegal under SCD and I eat it because my gut says it’s okay. It’s probably no coincidence that many of these things are food to the friendly bacteria in my colon. I am now more concerned about feeding my little bacterial buddies than I am about feeding myself. Maybe if my gut heals up and my gut bacteria recover, I’ll be able to reintroduce what I’ve had to cut out, but I still think that’s way over the horizon for me. Till then I’ll stick to the fibre and complex carbs.

What does your gut tell you?

The Gut Following Antibiotics: My uBiome Results

That cannot be right!

That was my first reaction when I saw my uBiome results. Having just come off almost a year of potent antibiotics, I had prepared my eyes to view a ragged, threadbare landscape, but what I saw – glaring problems aside – was diversity!

Further detailed viewing has convinced me that the results are accurate.  They need to be nurtured as some genera of bacteria are only hanging on by their pilitips [erm, is that a new word? I’ll be covering neologism – the creation of new words – in my next post] but the bacteria are still there. It’s possible for me to reclaim my gut!

Context

I have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease which is strongly linked with poor gut health. I could go on and on about that, but instead I will just point out that the world renowned virus-hunter, Professor Ian Lipkin (think West Nile virus, SARS and Ebola) believes the cause will be found in the gut, and a crowd-funding campaign is under way to raise the $1.3 million needed to enable his team to do the work. Please do check out The Microbiome Discover Project for further details, and if you want a detailed understanding of the study then Simon McGrath does an excellent job in his article on Phoenix Rising.

antibiotic-bombI also have a suspected bacterial infection: Bartonella and Borrelia (Lyme disease) and as a result I endured almost a year of antibiotic treatment (Rifampin, Clarithromycin and Ketek) before which I had a gut flora test with Red Labs in Belgium.

While on the antibiotics I developed ulcerative colitis (UC) and lost 45lb over a few months. Standard treatment failed to make any difference (Mesalazine and Prednisolone) and eventually I decided to stop the antibiotics out of desperation. My weight lost halted immediately and I am slowly making a recovery.

It seems the antibiotics were a significant trigger of the UC and certainly perpetuated it. I took a uBiome test to see what damage the antibiotics did and now I’m trying to rebuild my gut.

Diet before the test

I have to admit that initially the improvement in my diet was not really by choice. When the UC hit, it came with significant intolerance to a variety of foods. I can no longer eat wheat/gluten, eggs, dairy (except cheese), maize, and almost all additives are out too. If I eat any of these then I have a strong and immediate flare. I eat oats and rice, meat and root vegetables. Some fruits are okay, some are not. A cup of tea of coffee will likewise leave me a wreck for a week, so I just drink water.

So I eat a lot more fibre than I used to and I no longer eat any junk at all. The only treat I have is dark chocolate, with no soya lecithin included, and this of course is an excellent pre-biotic. So I’m neither a healthy omnivore nor a Paleo-dieter, but perhaps somewhere in between the two.

Throughout the time I was taking antibiotics I was taking a pro-biotic supplement (Vitafytea bififlor forte).

Preparation for the test

I had been off the antibiotics for about a month when I took the Ubiome test. I knew I wanted to increase my dedication to my gut, introducing more fermented foods, pre- and pro-biotics, but I didn’t want to screw the results up and just see what was transient in my gut. So I held off introducing more until after the test. The results of this test will show me what the antibiotics left me with and only the very beginnings of my rebuilding.

I stopped the bifido pro-biotic supplement two days before my test. I had a pretty fast transit time at that point, so the results should be a pretty good reflection of what is at home in my gut, post anti-biotic treatment.

The results

As I mentioned already, before starting antibiotics I had a gut flora test with another company. This does allow me to make some comparisons, though being a test with a different company, with different processes, you have to take the comparisons with a pinch of salt.

Bacteria are grouped together at different levels (phylum, class, order, family and genus).  My top 5 phylum-level gut bacteria are shown in the chart below, and the grey-scale image shows the same from my earlier Redlabs test. Note that the ‘Average’ column is based on uBiome’s entire database, including both healthy and unhealthy folk, so may be somewhat misleading.

Phylum

The average given is from uBiome’s ‘healthy omnivore’ data.

Bacteroidetes are normally considered to be quite resistant to antibiotics, but mine have more than doubled. And firmicutes, which are normally thought to increase under antibiotics, and thrive when fed fibre, have instead decreased. You can see why my initial reaction was to think something was wrong with the results.

But the real interest, for me at least, is at the deeper levels. At the genus level for instance, I found that I have a dozen bacteria that are way below the normal average, either right at the bottom end of the range of ‘normal’ results, or below.

uBiome are still developing their visualization tools, as well as the size of their database, so in the future it’ll be possible to see how results compare to others that have taken antibiotics, but unfortunately this is not possible just yet. For now, I’m comparing my results to ‘Healthy Omnivores’ and ‘Paleo Dieters’ as seems most appropriate.

Here is a typical example:

Pseudobutyrivibrio_example

This suggests to me that the antibiotics did some damage and the additional consequence is that the genera of bacteria that are more prominent, as a percentage look very large, but not necessarily because their numbers are truly that high but because there’s a lot else missing, skewing the results.

When I test again, later in the year, I’ll be interested to see if these under represented bacteria stage a recovery and that’ll be the focus when I look at this next time. This time though, I’m going to point out a few other things that stick out.

Bacteroides

Research on Bacteroides is mixed; whatever your view, it’s pretty easy to find a study or two to support it. Some species subclasses are known to be enterotoxigenic and are associated with colitis (Rabizadeh S et al). Given the normal healthy average reported by uBiome is one third my reading, this does leave me wondering if this might be a significant factor in my developing colitis, especially when you bear in mind that my pre-antibiotic test with Redlabs showed a much lower reading of 12.58%. I’d be interested to hear what readers think of that.

Bifidobacterium

Not bad. My Redlabs test reported zero. The Redlabs test appears to be set-up to look for overgrowth rather than undergrowth, so I think the zero reading really meant close to zero. In any case, I have a healthy level now which is likely a combination of supplementation and diet improvement. I hope to increase this further as most research concludes that Biffidobacteria are a keystone of gut health, with other genera of bacteria feeding off the by-products of this bacteria (De Vuyst L et al).

RoseburiaSpecies of Roseburia are known to produce butyrate, which is thought to protect against colitis, so you’ll understand this is one I hope will thrive in my new gut. It certainly ought to represent more of my gut than it currently does.

Rumnococcus

Ruminococcus should thrive under a diet of resistant starch (Ze X et al). I hope so – as you can see it is rather lacking at the moment, and as I can’t tolerate lentils, beans or most grains, it looks like it’s going to be down to the resistant starch.

Faecalibacterium

I appear to have a more Faecalibacterium than normal, and this may be in part due to their love of resistant starch. One species of this genus, F. prausnitzii, is very abundant in all humans and its relative absence has been linked to Inflammatory Bowel Diseases (IBD). In unison with E.coli, it may even allow IBDs to be distinguished from each other and from those without such disease (Lopez-Siles M et al). 

What next?

My greatest fear was that some types of bacteria would be entirely absent, destroyed by the A-bombs I had dropped on them, but instead I find myself reassured; damage, yes, certainly; but gone all together? No. I have something to work with.

Since I took the test I have taken things a step further. I started growing my own vegetables. I wanted to increase my exposure to friendly soil-based organisms. Working an organic vegetable patch should help my gut, especially if I eat some raw, and ferment my own produce. I bought a fermenting crock and have already started eating home-made sauerkraut. I might write about the science of that if there is enough interest.

As well as this improvement in diet, I started taking various pro-biotics. Mutaflor (a friendly E.coli strain) has been shown to maintain remission in UC, and I bought the strongest bifidobacterium powder I could find from Custom Probiotics. And in light of my results, where an appropriate pro-biotic is available, I intend to start ingesting some, and the CFSRemission blog has some good information on probiotics – the problem is that the probiotic market only represents a narrow range of the different types that should live in your gut.

My diet is already pretty high in resistant starch as I eat a lot of green bananas, cooked-and-cooled potatoes and rice. But having read a lot of good about resistant starch on Phoenix Rising and on Mr Heisenbug, I introduced it as a supplement as well. I also added a FOS supplement and tried apple pectin powder too, but found this hard to swallow. My next test, which I will probably take in a couple of month’s time, will give a much better picture of my attempt to rebuild as it’ll reflect these additions.

So do I think a uBiome test was worth it? It’ll be really good once they’ve developed their tools and algorithms a bit further, but yeah, I reckon it was a very good purchase. You can buy yourself a kit from their website, but before you do, please consider making a donation to the Microbe Discovery Project – the millions of people with ME/CFS have waited a long time for a top scientist to take an interest, but without any government funding, they need your help.

You can follow my blog if you want to see my next results when they come in (buttons at the top of the page). If you’ve got any tips, observations, or questions, please leave a comment below.