A Fecal Matter Transplant goes wrong (several cases)

A reader sent me an email shown below:

…did a NirvanaBiome test before and 4 weeks after finishing the FMT. As far we can see her gut condition only got worse.”

On The Gut Club: Stool Test Discussion Group Facebook group, some other comments were shared

My first goal is to try to understand what went wrong and how. Then looking at “where do we go from here”. Ending with a reading list on FMT.

Additional Personal Experience with FMT shared

Analysis of Changes

I started with comparing Bacteria/Taxonomy Out of Range Over Time which showed 63 items. The most interesting are below. Percentile means where in a collection of 2000+ samples that the reading is. For example 97%ile means that 60 samples had more than this and 1940 samples has less – most people would deem that to be an excessive overgrowth. Prior means before the FMT, After means weeks after the FMT.

Bacteroa	Prior Percentile	After Percentile
(class) Clostridia	97.8	99.3
(class) Gammaproteobacteria	95.4	none
(family) Lachnospiraceae	95.8	none
(family) Ruminococcaceae	none	100
(genus) Ruminococcus	99,8	100
(order) Enterobacterales	97	none
(species) Ruminococcus bicirculans	none	100%

Nirvana data structure has some issues converting to string NCBI hierarchy/

My initial thought on seeing these results was – are we using the same lab? We are.

The mechanism of getting names is finding patterns in the raw data. Lachnospiraceae and Ruminococcaceae are both children of Clostridiales, so we may have

Clostridiales requires 100 matches
- Lachnospiraceae requires these matches and 20 more
- Ruminococcaceae requires these matches and 15 more
- There may be 8 matches in common with these two

This dramatic shift may be (1) a defect in the classification algorithm or (2) a bug in my specific import routine for CosmosId [which I am looking at) or (3) sibling families taking over [siblings tend to like the same environments] , I am inclined to the first cause(1) since the data is pushed through the same code(2) but (3) is almost as probable as (1). See my 2019 The taxonomy nightmare before Christmas… post for background.

Pie Charts

The two charts below show the growth of Clostridiales and the reduction of every other order. I have often described Fecal Matter Transplants as equivalent to an Organ Transplant (or Blood Transfusions) with the same issues of rejection being significant. We do not know yet now to “type” or test the new item for compatibility.

I speculate that there may have been warfare with several orders weakened, Clostridiales was already near an extreme value — my gut feeling is that bacteria with strong overgrowth are dominated by strains that have the following characteristics

They are more robust (i.e. more resistant to bacteriocins (natural antibiotic) produced by other bacteria
They produce significantly more strong bacteriocins

The diagram below helps to explain bacteriocins. It show different strains of Lactobacillus Reuteri. Reuterin is the bacteriocins(natural antibiotics) produced. Some produce a high amount, some a low amount and others none.

From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillusreuteri have diverse probiotic functions[2014].

Drilling down into Clostridiales we see major shifts. CosmosId report by strains, so these numbers are reliable

What we see ins that one species EXPLODED, Ruminococcus bicirculans. Prior to the FMT, it’s count was 47,810 or 0.5%, after it jumped to 444,900 (44.5%!!!) – a 10x increase. Whether it was a new strain that was introduced by the FMT that the existing microbiome could not handled as well as the donor (I deem more likely) or an existing strain that filled the vacuum resulting from the FMT bacteria and native bacteria wiping each other out (less likely) is speculation.

Suggestions

We have an idea of what may happen, apart from being a visual warning in the above diagrams to people considering FMT. The key question for this person is how to undo it. For this troublesome strain, we know some things that will increase or decrease it. I would focus on this strain alone and do a deep “spring cleaning” of supplements.

Looking at the Kaltoft-Moltrup Range based suggestions, we see a lot of bacteria selected as abnormal

And we see most of the above items are on the suggestions for this combination:

Bottom Line

I would suggest (after reviewing with your medical professional) the above changes and then do another Nirvana sample after 6-12 weeks to see what has changed. I would expect this Ruminococcus bicirculans. to be significantly reduced, the question is what will replace the 44% of the microbiome it currently occupies.

I was curious if we could infer something about the donor by looking at these changes. I looked at life style that could impact Ruminococcus bicirculans. etc and found that

INCREASE: reduced calories low-carbohydrate high-fat diet [2021]
INCREASE: exercise-stress [2016]

A common sense (A priori) definition of what would be a healthy donor will often be someone that fits these two features, i.e. an athlete. ” Recent trends show more athletes trying a low-carbohydrate, high-fat (LCHF) diet for endurance performance. ” [Low vs. High Carbohydrate Diets for Endurance Performance] IMHO, this a priori common sense healthy donor is wrong — athletes have abnormal microbiomes. A priori is defined as “denoting reasoning or knowledge which proceeds from theoretical deduction rather than from observation or experience.“

The compatibility issue is not only at the microbiome but diet and exercise style. If the recipient does not consume the same diet as the donor, the transfer may go in odd directions. Similarly, we know exercise impacts the microbiome. A “desk jockey” getting the microbiome of someone that cycles for 4 hours a day will likely fade quickly.

Prior Posts on FMT

My interest in trying to understand different FMT responses go back at least 5 years. The following posts are likely worth reviewing. My feeling continues to be that the downside risk for the upside benefit is still too low to be a desirable course of action. Typically, it is an improvement that does not persist for extended periods. I believe a committed microbiome manipulation with regular retests and adjustment has considerably less downside and equivalent upside benefit that will likely persist longer — especially, if at least two samples and adjustments are done a year once sufficient benefit has been obtained.

Different ways of Doing FMT

I am tossing some technical information for those that are interested in how FMT can be done. There are many ways, including “the turkey baster” aka “Turd Burglars“. IMHO, it should be done under medical supervision with adequate testing (including comparing the donor’s microbiome, and life style to the recipient)

By Enema

This was used by the above

FMT with Enema – 6 doses, 1 every other day (11 days)

No antibiotics are used!

Pre- and probiotics (phgg, bifido)

Prior

Do not stop medication
follow a liquid diet the night before the first administration (and not the other 5!!!)
cleansing water enema in the morning before FMT
place the dose from the freezer in the refrigerator the night before. allow the dose to reach room temperature in the morning.
swallow 1 imodium after awakening (only) for the first dose
limit yourself to a light (liquid) meal

During

do not eat or drink anything during and immediately after the enema.
work in stages with a limited dose (but within 10 minutes on the left side)
use gravity to keep everything inside, e.g. a pillow under the hip
take a few deep breaths regularly
alternate position (left side, back, stomach, right side), every ten minutes (left is best for keeping inside)
regularly massage the dose upwards gently
try to keep the dose for ideally more than 6 hours
rest, relaxation and sleep are the best activities during the therapy days

After

do not immediately make major changes to your daily diet
not drinking and being (somewhat) thirsty helps to withdraw fluid from the injected dose
fibers help the new bacteria to settle. gradually introduce fiber into your diet. fiber rather through food than supplements.

Centre for Digestive Diseases – Doctor Thomas Borody

” Dr Borody has overseen over 12,000 FMTs, creating a wealth of proprietary clinical data and insights.” Antibiotics are frequently used prior to FMT. He is likely the leading Australian MD that does FMT.

Faecal Microbiota Transplantation
- ” published response rates in some studies using FMT to treat UC greater than 50%¹.”
- “In our experience FMT may help symptoms of Irritable Bowel Syndrome (IBS) however, this not guaranteed. “

Selected publications

Faecal microbiota transplantation alleviates symptoms of depression in individuals with irritable bowel syndrome: A case series
Response to article “A retrospective outcome study of 42 patients with chronic fatigue syndrome, 30 of whom has irritable bowel syndrome. Half were treated with oral approaches, and half were treated with faecal microbiome transplantation”
Evolution of fecal microbiota transplantation in methodology and ethical issues
Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer
Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study
Fecal microbiota transplantation: A ‘How-To’ guide for nurses
- “Mild and transient side effects reported with the procedure include abdominal cramping, dis-comfort and bloating, belching, diarrhea, constipation, nausea and flatulence, which can occur while the infused bacteria are establishing themselves. A case of worsening inflammatory bowel disease, two cases of norovirus gastroenteritis and one case of E. coli bacteremia have also been reported, however FMT could not be established as the cause of these events” — NOTE The defensive “could not be established as the cause of these events” interpretation

There are more publications on his website.

Bacteria influencing other Bacteria

Recently I revisited finding association between bacteria. We know bacteria both produce and consume metabolites and chemicals, as well as bacteriocins that will inhibit other bacteria. “Bacteriocins are potential alternatives to traditional antibiotics. These peptides, which are produced by many bacteria, can have a high potency and a low toxicity” {Nature 2012]. Finding the relationships has been a challenge because of the nature of the distribution (not a bell curve — see this post on the solution that I use for identifying abnormal values) Post #1 Post #2.

This is a technical note (WARNING: Geek Speak) on the 262,603 relationship with correlation coefficient R² of 0.10 or higher that is available on the site.

Example of Classic Association

For our example, we will compare two families: Brucellaceae and Caulobacteraceae. Their ancestry is shown below

Because they have some shared ancestry, you would usually expect them to be friendly and suppurative of each other. The standard analysis is shown below, charting the counts from samples that have both bacteria.

Classic Approach

After an intro course to statistics, most people would do a regression. It is unlikely they would look at the chart because there are 2,669,956 charts that would be produced with the dataset that I am working with.

The regression and the chart is shown below, logical conclusion – no relationship.

Each axis is the count of a specific bacteria (Brucellaceae and Caulobacteraceae) from the same sample.

Alternative Approach

The alternative is to use what is called monotonic increasing functions on the counts. We scale the function so that it’s range is 0 to 100. This preserves the nature of the data and discard the naïve assumption of linearity. The result is shown below. With this approach, we get the following chart. same data!!!

Each axis is the transformed count of a specific bacteria (Brucellaceae and Caulobacteraceae) from the same sample.

We could for each pair of bacteria derive the absolute optimal monotonic functions. This approach I find problematic because your appear to be fiddling with the data too much. I have put the additional constraint that you are allowed only one monotonic function per bacteria. I believe this will inhibit over-fitting the data to the model.

How many relationships over 0.1?

We have 1621 bacteria with at least one, and the top ones are shown below

taxonomy rank	taxonomy name	Count
family	Halanaerobiaceae	546
class	Fibrobacteria	526
class	Dehalococcoidia	506
family	Fibrobacteraceae	505
order	Fibrobacterales	501
genus	Fibrobacter	483
family	Nitrosomonadaceae	474
genus	Dehalogenimonas	474
order	Acidobacteriales	467
family	Micromonosporaceae	461
genus	Nitrosomonas	460
genus	Acinetobacter	459
family	Colwelliaceae	455
family	Acidobacteriaceae	453

What benefit does this give?

The impact of one bacteria on the other may be computed as slope * r² . So R² of .5 and a slope of .4 = .5 * .4 = .20 or 20%, thus for every 10 steps of one, the other will increase by 2.

We can use this when some bacteria X is high or low and we have no information on modifying it. We can look at the related bacteria with highest impact and its modifiers. We are trying to cascade by changing the associated bacteria to change our target bacteria! We are attempting to model the modifiers secondary changes into our suggestions.

Where is this on the site?

On the bacteria details pages. if there are associations, there will appear a link to it

Clicking this will take you to the impact page. In the example below you see that Lactobacillus accounts for 63% of it’s parent class. Lactobacillaceae(family) which includes Lactobacillus , Pediococcus , and Sharpea. So it is the greatest contributor the three.

Orphan Detail Pages

I call these orphan because there is not literature on them or little studies. For example Pectinatus where there was just one know citation, ginko. We now have 10 more marked with the association icon as shown below.

Available to include for Suggestions

There is a new checkbox on the custom suggestion page. If you wish these to be factored into suggestions just check the box.

Reviewing the impact of Ivermectin and Nystatine

A reader asked for a review. The reader had a prior sample taken 6 weeks before and specific treatments between

I took Ivermectin for 4 days during this month – one per day 12mg. I am treating yeast with nystatin 5,000 units 2 times per day for one month. I hope the die-off may have made room for bacteria to grow. I still feel crappy. I stopped lactobacillus ( I tried Lactobaciullis grains from Keith during that time. too much bloating), and started Akkermansia muciniphila and very recently some Bifidobacterium. I had cut back on dairy earlier (using soy milk and oat milk instead). I also took Sporonax (Itraconazole) antifungal about 5 times and Valtrex 500 mg 8 times.

My starting point (before looking at the samples) is to look at what we know about the impact of these items.

nystatine,(prescription) – of the 1286 bacteria listed, it decreases ALL of them
ivermectin,(prescription) – of the 1286 bacteria listed, it decreases ALL of them
itraconazole,(prescription) – of the 1286 bacteria listed, it decreases ALL of them
valacyclovir hydrochloride,(prescription) (Valaciclovir, Valtrex, Zelitrex) – of the 1286 bacteria listed, it decreases ALL of them

So the expectation of making room for bacteria appears very reasonable. The unfortunate aspect is that among the causalities are: Lactococcus, Lactobacillus, Bifidobacterium and Akkermansia muciniphila. So the question arises, will the good or the bad grow back faster?

What changed?

I first checked the common bacteria that most people are usually concerned with (cited above) and then will look at what increased. One item is of definite concern 💥, (class) Fusobacteria

Bacteria	Before	Latest
(genus) Lactobacillus	1150	⇲140
(genus) Lactococcus	380	⇲180
(genus) Bifidobacterium	640	⇲340
(species) Akkermansia muciniphila	50	⇲30
(species) Hathewaya histolytica	220	⬆️869
(class) Negativicutes	10090	⬆️14820
(class) Gammaproteobacteria	790	⬆️1500
(class) Bacteroidia	267,859	⬆️322,050
(class) Chitinophagia	20	⬆️70
(class) Fusobacteria	55280	⬆️90210 💥
(class) Coriobacteriia	3160	⇲670
(class) Sphingobacteriia	1010	⇲270

Checking back with what is decreased by the drugs, at the family level

(family) Oceanospirillaceae had the largest increase, and is not listed as one that decreases
(family) Clostridiales Family XIII. Incertae Sedis, the same
(family) Clostridiales incertae sedis the same
(family) Acidaminococcaceae the same
(family) Hungateiclostridiaceae the same
(family) Alcaligenaceae the same
(family) Fusobacteriaceae is listed as a should decrease, but it increased — it should be noted that this was very high in the prior one and more resistant and thus increased when the vacuum was created,
(family) Bacteroidaceae the same

It was interesting to note the many of the bacteria that were abnormally high (95%ile) stayed the same or increased. The fact that they were high implies more aggressive strains (and possibly more bacteriocin and antibiotic resistant).

Looking at species that are outside of the KM range, we have the following being excessively high

Note that other Blautia species were abnormally low. These are already accounted for in the suggestions.

Looking further back

“I believe vancomycin started the problem to flare when I took in a couple of years ago. I also had my first covid shot of June 26, 2021 with immediate bad reactions and probably made worse since.

vancomycin (antibiotic) Increases some and decreases other

The very high Fusobacteria identified above is one bacteria that would be decreased by this antibiotic (so this is unlikely that this the cause of this being high).

The following are items that have been reported to increase this bacteria:

Suggestions

I expect the suggestions to be very similar because the items high before stayed high (i.e. no change)

There was one additional probiotic suggested from the latest sample and it had a far stronger impact then the older ones.

The KEGG suggested probiotics are the same ones, just a higher value because of an increased deficiency in enzymes being produced by the microbiome.

Bottom Line

The data base correctly predicted the likely decrease of the common bacteria assumed important for health. Those that did no reduce were either not effected, more resistant strains (inferred from being high numbers prior)

What I found interesting was the absence of most probiotics (lactobacillus and bifidobacterium) in the safe suggestions, except for bifidobacterium breve. Securil (Propionibacterium freudenreichii) probiotic came in very strong.

Giloteaux⁶⁵ found that supplementation with the bifidogenic substance Propionibacterium freudenreichii improved butyrate levels, which induces an anti-inflammatory cascade [2017]
One of particular interest is found in the product Securil and is called – Propionibacterium freudenreichii, which produce propionic acid, a natural biological acid that benefits the bifidus flora. [2010]
More studies here

Note that this is specific for this person. Suggestions will be different for other peoples taking the same items.

Reader’s Desire

“I was also trying to get my methylation working better and taking b vitamins again. Could it be the b vitamins?”

The B-vitamins are suspect for the high levels of Fusobacteria. We should also note that are the to avoid list we see many of the B vitamins which suggests that much of the dysbiosis may be vitamin B related.

Concerning methylation, I usually see what enzymes are involved by checking with the Kyoto Encyclopedia of Genes and Genomes, And then check the KEGG Enzyme Outliers report. This report had a very high 470 items listed!!

A few of outliers showing extreme values

Drilling down into a few, we see some of the causes

This value is beyond the K-M range and thus suggestions to correct this is automatically captured in the above suggestions.

Example of Microbiome manipulation for hypertension

After a recent hospital visit for cellulitis (with many different antibiotics, both orally and by IV), my blood pressure was significantly elevated that the substitute MD (my usual was on vacation), that I was put on Lisinopril. Within a week I developed a dry cough that has for 35 years has been a “tell” for a relapse into Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Checking the literature, I found that about 30% of people develop this cough. To me it is an important tell, if it shows up — I need to do quick re-examination of what is going on. For a prescription drug to do so, really made me uncomfortable.

I then check Lisinopril against the bacteria shifts reported for ME/CFS, and it made them worst. In short, staying on it may well increase the risk of relapsing into ME/CFS. That is not acceptable.

I did a little more research and found a variety of different opinions on COVID and the use of ACE2, one example is Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France, 2020

In 2019, I had done a posting on hypertension citing Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document. [2019].

I stopped the lisinopril and proceeded to take the nutrients etc cited above, at or above the specified dosages. I know that it will take a little time for the microbiome to respond, but it did.

The spikes were from not waiting long enough after exercising. I now rest at least 20 minutes

Bifidobacterium Correlation

Reviewing the literature, there is the appearance of blood pressure being strongly associated with the amount of bifidobacterium as we age. Children are very high in Bifidobacterium and low in BP. As the typical amount of bifidobacterium decreases with age, blood pressure increases.

I found this recent study,

The effect of dietary fiber (oat bran) supplement on blood pressure in patients with essential hypertension: A randomized controlled trial [2021] “Increased DF (oat bran) supplement improved BP, reduced the amount of antihypertensive drugs, and modulated the gut microbiota. The use of antihypertensive drugs in the DF group was significantly reduced. The changes[increase] of Bifidobacterium and Spirillum in the DF group were significant.”

As a result, I add 2 tablespoons of bran to the typical 4 table spoons of oats porridge that was doing. I also added a package of Holigos (Human Milk Oligosaccharides) which I know is a super feeder of bifidobacterium.

This corresponded to the severe drop shown above.

Possible Probiotic Impact

I was taking the following based on modelling of the bacteria shifts seen in hypertension:

Samples are coming…

Just got notification from the lab that last weeks was received.

One addendum, when I was in hospital for cellulitis, my potassium was very low and I required a (painful) IV of potassium. I examined the amount of potassium that my usual diet provided… It was very low, so I started to supplement with potassium citrate also.

Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials [2017]

Bottom Line

I was able to normalize (for an almost 70 year old) blood pressure by using existing research and having patience. I believe the key items was encouraging bifidobacterium growth (sorry, bifidobacterium probiotics do not persist usually and have little impact), correcting mineral content (potassium, magnesium, calcium).

One more addendum, I usually did 10,000 steps a day with weekend hikes often being as high as 20,000 steps.

Hypertension and Probiotics

In an earlier post I cited supplements demonstrated in human clinical trials to lower blood pressure. A still earlier post looked at gut bacteria associated with hypertension and hypotension. I have collected the bacteria shifts reported from studies published on PubMed here

Literature of the microbiome bacteria

The following are the sources for the bacteria information

Administration with Quinoa Protein Reduces the Blood Pressure in Spontaneously Hypertensive Rats and Modifies the Fecal Microbiota.
Nutrients (Nutrients ) Vol: 13 Issue 7 Pages:
Pub: 2021 Jul 17 Epub: 2021 Jul 17 Authors Guo H , Hao Y , Fan X , Richel A , Everaert N , Yang X , Ren G ,
Summary Html Article Publication

Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats.
BMC microbiology (BMC Microbiol ) Vol: 21 Issue 1 Pages: 141
Pub: 2021 May 5 Epub: 2021 May 5 Authors Li L , Zhong SJ , Hu SY , Cheng B , Qiu H , Hu ZX ,
Summary Html Article Publication

Improvement of intestinal flora: accompany with the antihypertensive effect of electroacupuncture on stage 1 hypertension.
Chinese medicine (Chin Med ) Vol: 16 Issue 1 Pages: 7
Pub: 2021 Jan 7 Epub: 2021 Jan 7 Authors Wang JM , Yang MX , Wu QF , Chen J , Deng SF , Chen L , Wei DN , Liang FR ,
Summary Html Article Publication

Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study.
European heart journal (Eur Heart J ) Vol: 41 Issue 44 Pages: 4259-4267
Pub: 2020 Nov 21 Epub: Authors Verhaar BJH , Collard D , Prodan A , Levels JHM , Zwinderman AH , Bäckhed F , Vogt L , Peters MJL , Muller M , Nieuwdorp M , van den Born BH ,
Summary Html Article Publication

Changes in the Gut Microbiota are Associated with Hypertension, Hyperlipidemia, and Type 2 Diabetes Mellitus in Japanese Subjects.
Nutrients (Nutrients ) Vol: 12 Issue 10 Pages:
Pub: 2020 Sep 30 Epub: 2020 Sep 30 Authors Takagi T , Naito Y , Kashiwagi S , Uchiyama K , Mizushima K , Kamada K , Ishikawa T , Inoue R , Okuda K , Tsujimoto Y , Ohnogi H , Itoh Y ,
Summary Html Article Publication

Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study.
Scientific reports (Sci Rep ) Vol: 10 Issue 1 Pages: 14771
Pub: 2020 Sep 8 Epub: 2020 Sep 8 Authors Groot HE , van de Vegte YJ , Verweij N , Lipsic E , Karper JC , van der Harst P ,
Summary Html Article Publication

Differential Analysis of Hypertension-Associated Intestinal Microbiota.
International journal of medical sciences (Int J Med Sci ) Vol: 16 Issue 6 Pages: 872-881
Pub: 2019 Epub: 2019 Jun 2 Authors Dan X , Mushi Z , Baili W , Han L , Enqi W , Huanhu Z , Shuchun L ,
Summary Html Article Publication

Critical Role of the Interaction Gut Microbiota – Sympathetic Nervous System in the Regulation of Blood Pressure.
Frontiers in physiology (Front Physiol ) Vol: 10 Issue Pages: 231
Pub: 2019 Epub: 2019 Mar 8 Authors Toral M , Robles-Vera I , de la Visitación N , Romero M , Yang T , Sánchez M , Gómez-Guzmán M , Jiménez R , Raizada MK , Duarte J ,
Summary Html Article Publication

DIFFERENCES IN MICROBIOME IN RAT MODELS OF CARDIOVASCULAR DISEASE.
South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie (S Afr J Surg ) Vol: 55 Issue 2 Pages: 71
Pub: 2017 Jun Epub: Authors Thiba A , Umar CA , Myende S , Nweke E , Rumbold K , Candy G ,
Summary

Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension.
Hypertension (Dallas, Tex. : 1979) (Hypertension ) Vol: Issue Pages: HYPERTENSIONAHA11914294
Pub: 2020 Feb 24 Epub: 2020 Feb 24 Authors Kim S , Rigatto K , Gazzana MB , Knorst MM , Richards EM , Pepine CJ , Raizada MK ,
Summary Publication Publication

Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.
Circulation research (Circ Res ) Vol: Issue Pages:
Pub: 2020 Feb 13 Epub: 2020 Feb 13 Authors Yan X , Jin J , Su X , Yin X , Gao J , Wang X , Zhang S , Bu P , Wang M , Zhang Y , Wang Z , Zhang Q ,
Summary Publication Publication

Exercise and food supplement of vitamin C ameliorate hypertension through improvement of gut microflora in the spontaneously hypertensive rats.
Life sciences (Life Sci ) Vol: 269 Issue Pages: 119097
Pub: 2021 Mar 15 Epub: 2021 Jan 19 Authors Li Y , Zafar S , Salih Ibrahim RM , Chi HL , Xiao T , Xia WJ , Li HB , Kang YM ,
Summary Publication

Enterococcus faecalis contributes to hypertension and renal injury in Sprague-Dawley rats by disturbing lipid metabolism.
Journal of hypertension (J Hypertens ) Vol: 39 Issue 6 Pages: 1112-1124
Pub: 2021 Jun 1 Epub: Authors Zhu Y , Liu Y , Wu C , Li H , Du H , Yu H , Huang C , Chen Y , Wang W , Zhu Q , Wang L ,
Summary Publication

Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother ) Vol: 140 Issue Pages: 111736
Pub: 2021 Aug Epub: 2021 May 23 Authors Lakshmanan AP , Shatat IF , Zaidan S , Jacob S , Bangarusamy DK , Al-Abduljabbar S , Al-Khalaf F , Petroviski G , Terranegra A ,
Summary Publication

Gut microbiome diversity and composition is associated with hypertension in women.
Journal of hypertension (J Hypertens ) Vol: Issue Pages:
Pub: 2021 May 10 Epub: 2021 May 10 Authors Louca P , Nogal A , Wells PM , Asnicar F , Wolf J , Steves CJ , Spector TD , Segata N , Berry SE , Valdes AM , Menni C ,
Summary Publication

Probitotics

From Theoretical Model

These are based on the bacteria reported above and an AI engine on the impact of various probiotics (in order of confidence). Links to dosages found to be sufficient to cause changes in clinical trails are after each. It is a common mistake to take ‘homeopathic” dosage, that is, if a product contains one of these, then that is sufficient. This thinking is akin to thinking that a squirt gun is sufficient to put out a wildfire!

bacillus subtilis (probiotics) 📏🍽️ Dosages — Confirmed in Animal Studies
lactobacillus rhamnosus (probiotics) 📏🍽️ Dosages – Animal studies
lactobacillus plantarum (probiotics) 📏🍽️ Dosages -slight impact sometimes
lactobacillus reuteri (probiotics) 📏🍽️ Dosages
lactobacillus acidophilus (probiotics) 📏🍽️ Dosages
saccharomyces boulardii (probiotics) 📏🍽️ Dosages
bifidobacterium bifidum (probiotics) 📏🍽️ Dosages
bifidobacterium longum (probiotics) 📏🍽️ Dosages
lactobacillus casei (probiotics) 📏🍽️ Dosages

From Animal Studies

Often animal studies do NOT replicate to humans, so care need to be taken. Where it available, the strain is give with a link to the study.

Lactobacillus fermentum CECT5716 (LC40) [2021]
Bifidobacterium breve CECT7263 (BFM) [2021]
” The fermentation of beans with Bacillus Subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.” [2014]
“water extracts of Bacillus subtilis-fermented pigeon pea (100 mg/kg body weight) significantly improved systolic blood pressure (21 mmHg) and diastolic blood pressure (30 mmHg) in spontaneously hypertensive rats.” [2015]
” treatment of model rats with Lactobacillus rhamnosus GG prevented aggravation of hypertension by reducing blood TMAO levels, modulating Th1/Th2 cytokine imbalance and suppressing phosphorylation levels of ERK1/2, Akt and mTOR.”[2019]

From Human Studies

NO EFFECT from Lactobacillus plantarum PS128 [2031] -dosage was sufficient
- “The clinical significance of blood pressure-lowering effect of Lactobacillus Plantarum supplementation is not considerable; ” [2020]
- “Our meta-analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension, particularly in those with diabetes mellitus, following probiotic supplementation. This effect was associated with treatment duration, dosage, and the age of subject but was not associated with single or multiple strains usage. Additionally, probiotic supplement had a beneficial effect in reducing BMI and blood glucose.” [2020]
“Lactobacillus consumption significantly reduced systolic blood pressure (SBP) by -2.74 mmHg and diastolic blood pressure (DBP) by -1.50 mmHg when comparing with the control group.” Dosage above 5 Billion CFU per day. [2020]
“Probiotic consumption significantly changed systolic BP by -3.56 mm Hg and diastolic BP by -2.38 mm Hg compared with control groups.” After 8 weeks at 10+ Billion CFU/day [2014] No strains or species specified
“Lactobacillus para casei LPC-37, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM, and Bifidobacterium lactis HN019 (109 CFU of each strain) for 8 weeks….Probiotic supplementation lowered, although without statistical significance, systolic BP by about 5 mmHg and diastolic BP by about 2 mmHg in hypertensive women.” [2020]
Saccharomyces boulardii – no effect [2012]
Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus [2021] — this does not mean the probiotics will have significant effect because bifidobacterium rarely persist and are gone in hours. However, the consumption of oat bran, reduces BP and increases bifidobacterium [2021]

Bottom Line

Bacillus subtilis (especially the Natto strain) appears to be most effective, both from a theoretical and animal study point of view. The theoretical model appears to work reasonably. Probiotic consumption appears to do no harm from clinical studies — however, the theoretical model indicates some may increase the microbiome shifts in the wrong direction.

Using supplements and changing diet (i.e. having oat bran daily) will have a far greater impact.

Hypertension – Including 3-legged-stool model

This post is an update of an earlier post. It deals mainly with non-prescription items. Some prescription items can have adverse effects on the microbiome seen with other conditions. “No medical condition is an Island“

After reviewing reviewed tested supplements, we use the Three-Legged-Stool model to get additional candidates and then check if there are studies supporting their use.

Prescription Responder and Non-Responders

I came across this 2021 article that was investigating DNA/SNP and hypertension drugs.

“Drug effectiveness was defined as 10% decrease in systolic blood pressure at 1 week follow-up. “
Genomic markers associated with successful treatment of hypertension with lisinopril: A pilot study [2021]

If you do not see that type of response, there may be genetics involved.

Base List

This base list comes from my 2019 review, “Hypertension – What we know” with most items coming from Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document. [2019] All of these are based on actual human clinical studies and not on rodent studies. See above for amount of impact for each substance. Current studies suggests that impact is linearly cummative.

Pycnogenol	100–200 mg
Lycopene	15–50 mg
Melatonin	2–5 mg
Coenzyme Q10	100–300 mg
Resveratrol	>300 mg
Magnesium	500-1000mg
Cocoa flavonoids	200 mg
Calcium	1500–2000 mg
Potassium	4–5 gr
L-Arginine	10-20 gr
Taurine	1-2 gr
Quercetin	150 mg [2009]

Additional items are discussed in Role of natural herbs in the treatment of hypertension, 2011, but with less critical review.

Candidate Modelled Substances

For modelling substances for a condition, I often use a three legged tool as shown below

Items were ranked by number of bacteria favorability impacted. The top 3 suggested modifiers are below. The next step is to see if there is any literature. [Good Impact: Bad Impact]

resistant starch [12:6]
- Trial using it [2021]
- 3.3 mm HG drop in DBP (no change in SBP) [2019]
berberine [12:10]
- Studies suggests lowering [2021]
Slippery Elm ( Ulmus macrocarpa ) [11:4]
- Lowers in Rodent studies [2008]

The next 4 items contains one surprise – licorice is usually associated with increase of BP

lactobacillus plantarum (probiotics) [9:7]
- Reduced mean arterial pressure [2021]
- Effect of Lactobacillus plantarum containing probiotics on blood pressure: A systematic review and meta-analysis [2020]
- “A statistically significant reduction in systolic blood pressure was also observed”[2017]
glycyrrhizic acid (licorice) [9:8}
- “Women taking licorice have experienced elevated blood pressure” [2021]
- ” No electrolyte abnormality, significant changes in blood pressure or blood glucose levels were observed during the [Licorice] study.” [2019]
- appear to cause hypertension in association with potassium chloride [2018]
rosmarinus officinalis (rosemary) [9:1]
- “Both blood pressure variables of SBP and DBP reflect the clinically significant antihypotensive effect of Rosemary essential oil that was maintained throughout the treatment period. ” [2014]
fructo-oligosaccharides (prebiotic) [9:6]
- Nothing

The next items

zinc [8:3]
- “Angiotensin-converting enzyme (ACE) is a zinc-dependent dicarboxypeptidase ” [2021] – impacts prescription hypertension medicines
- “Zinc and copper might be not independently associated with hypertension in US adults.” [2018]
saccharomyces boulardii (probiotics) [8:3]
- nothing
wheat [8:1] – complex, ancient varieties appear to have benefits
- “Antihypertensive and antioxidant activities of enzymatic wheat bran protein hydrolysates” [2020]
- Short-Term Hemodynamic Effects of Modern Wheat Products Substitution in Diet with Ancient Wheat Products: A Cross-Over, Randomized Clinical Trial [2018] SBP decreased
arabinoxylan oligosaccharides (prebiotic) [8:1]
- nothing
inulin (prebiotic) [8:2]
- Inulin Supplementation Reduces Systolic Blood Pressure in Women with Breast Cancer Undergoing Neoadjuvant Chemotherapy [2019] SBP: -4 mm Hg
lactobacillus salivarius (probiotics) [7:1]
- Nothing
vitamin a [7:2]
- Inverse association between dietary vitamin A intake and new-onset hypertension[2021] “Our results emphasized the importance of maintaining relatively higher vitamin A intake levels for the prevention of hypertension.”
oregano (origanum vulgare, oil) |[7:2]
- Nothing

We do see some items from our first list, with predictions tending to agree. Remember that we are doing a naïve count by bacteria and dealing with fuzzy data

quercetin [6:2]
resveratrol (grape seed/polyphenols/red wine) [6:5]
melatonin supplement [5:8]
magnesium [4:0]
Cacao [3:1]

Bottom Line

This illustrates the use of the three legged stool approach for treating conditions. The use of microbiome appears to produce an extended list of candidates substances that appears to be in general agreement with studies. Each candidate substance should be researched because we have a complex mixture of bacteria.

These modelled suggestions have been added to MicrobiomePrescription

Deep vein thrombosis and the microbiome

A reader emails as shown below. The deep vein thrombosis (DVT) aspect interest me because it is typically associated with inherited coagulation defects (an interest that I have), although actual DVT has not been an interest (when I flew regularly, I was prescribed heparin and took it with piracetam (good for my specific defect).

On 15 July 2021 I uploaded my first Thryve sample to your website. Prior to that sample I had a few Ubiome samples from a few years ago. Thryve seems to detect many more bacteria than Ubiome.
My results seem particularly unusual with numerous rare bacteria unfortunately. My main symptoms have always been constipation, food allergies and 2 episodes of DVT whereby I remain on anticoag therapy to avoid further recurrences.
Bacteroides Vulgatus seems to be significantly high in all of my test results, both Ubiome and Thryve. I wonder whether this could be the ‘root cause’ given that the numbers of it are so much higher than any other bacteria.

What is known about DVT and Microbiome?

After a while searching PubMed, I finally found a 2020 article. Of special interest is Staphylococcus aureus which appears to have a significant role with ME/CFS [2016 Post] and may account for the high percentage of hypercoagulation seen there.

” Many known bacteria, such as Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, causing infections may increase the risk of thrombotic complications through platelet activation or may lead to an inflammatory reaction involving the fibrinolytic system.” Microbial Modulation of Coagulation Disorders in Venous Thromboembolism [2020]

A fuller list from the full article (Citing 2019) is, below

Staphylococcus aureus,
Streptococcus pyogenes
Pseudomonas aeruginosa,
Escherichia coli,
Klebsiella pneumoniae,
Chlamydia pneumoniae,
Helicobacter pylori,
Haemophilus influenzae

Looking at samples over three year, we have a strong candidate for causing DVT, Haemophilus parainfluenzae. It is consistently very high. Blank indicated no reported value.

Bacteria	21-07-15	19-06-15	18-12-19	18-08-13
Staphylococcus aureus
Streptococcus pyogenes	71% for Streptococcus (most not classified)
Pseudomonas aeruginosa
Escherichia coli
Klebsiella pneumoniae
Chlamydia pneumoniae
Helicobacter pylori
Haemophilus influenzae/ Haemophilus parainfluenzae	94.6%ile	89%ile	91.2%ile	95.8%ile

Checking the microbiome prescription summary for this bacteria, we see a short list of herbs impacting it (there is bigger list of antibiotics)

Personally, I would start with wormwood, and then start drinking teas with the other ones.

Almost every probiotics encourages it. PPI, ku ding cha tea also increases t.

The sole exception is a probiotic available only in Italy.

Other items reported to decrease it are:

vitamin d

Personally, I would address this as #1 item.

Constipation

Using the Nat.Library of Medicine filter for constipation and relaxing to include high and low 12%, we came up with only a very short list of candidates. Using Kaltoft-Moldrup bounds, nothing was selected.

One study found Haemophilus influenzae associated with GI issues [2004]

As for allergies, “Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. ” [2009]

Running Advance Suggestions “as Is”

The key items selected reflects our analysis above:

KEGG Suggested Probiotics

The numbers are low, indicating no major issues. None of the suggestions are known to increase (or decrease) our focus. For supplements, it is similar

beta-alanine
NADH

Bottom Line

The primary question from the user appears to be answered. I would suggest fixing the Haemophilus parainfluenzae in isolation from the other two issues. Those two issues resolution will likely tend towards the use of probiotics — which are counter indicated with Haemophilus parainfluenzae. You have to prioritize issues and be careful not to send mix messages to the microbiome.

As always, review and consult with your medical professional before implementing

Getting bacteria for KEGG vectors

A reader sent me this email (actually another one did too). The issue was fixed but not in the obvious way:

Inline image — **BUG:** Checking and “Add elected items…”

This was actually a coding error, the checkbox should not be there. To do what the user intended:

Now to pick bacteria for KEGG Vectors

Below is the revised page fixing the problem. Notice the RED RECTANGLE

Clicking this will take you to the page listing the bacteria for this item, example below

On this page the checkboxes work. You see all of the bacteria associated that you have and thus can target the specific one (likely Brochothrix thermosphacta that is running well above the top of the normal range) that is causing the KEGG Vector (Product, Enzyme, Module) to be of concern.

Another Long COVID Microbiome

While working on the last long COVID post, another Long COVID person contacted me. He was definitely frustrated (in the same way that I have seen people with ME/CFS be frustrated over the last decades).

I’ve literally consulted with over 7 doctors (internist, hematologist, endocrinologist, ENT, GI specialist, cardiologist, & neurologist) over 3 weeks period and still have 4 consultations to go! All those doctors did is to request for more bloodwork and scans and then tell me that it’s all in my head (using smooth words) and send me home!
Long Haul Covid Patient

Recap on the Literature

The Microbiome and COVID have strong relationships. The microbiome prior to COVID impacts the severity. The severity of the symptoms correlates with the microbiome changes. This leads naturally to Long COVID being a continuation of this theme.

One study suggests that a core microbiota could predict COVID-19 severity in healthy subjects.²⁷ Another study shows that the composition of the intestinal microbiota in the Chinese cohort is different between COVID-19 infected and un-infected controls, with symptom severity correlating with specific bacterial taxa.²The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort [2021]

A new study used fecal samples were collected at least 38 days following diagnosis. By common belief, the patients are fully recovered — except their microbiome are not! What is the difference? It depends on where COVID presentation.

positive detection of SARS-COV-2 RNA from the respiratory tract, defined as respiratory positive (RP)
failure to detect in the respiratory tract, but had covid, is negative

They found changes in “13 phyla, 18 classes, 44 orders, 88 families, 234 genera, 1 phylum, 1 class, and 1 order were significant”. To put it simply, look at the changes below — they are NOT minor but major shifts!

This image has an empty alt attribute; its file name is image-35-1024x451.png — Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study [2021]

Our Long COVID Patient

My ongoing long haul symptoms:
– Vertigo/lightheadedness. Can’t maintain proper balance and head feels heavy 🙁 I was walking into furniture in my home! It’s difficult to drive a car or even fast walk or go down the stairs. I feel as if my head is heavy and will fall.
– Mood swings/anhedonia. No more feeling of happiness or pleasure. Low serotonin? Low dopamine?
– Brain fog/memory loss/loss of concentration. I’m back to work and it has been extremely difficult to get tasks done.
– Occasional blood in stool. Ulcers? Never had GI bleeding in my life!
– Early evening fatigue. Feel extremely tired past 8pm. I also wake up super early (5-6am) and can’t go back to sleep.
– Blurry vision during night.
– Slight shakiness/tremors in hands and legs. Low iron? Low dopamine?
– Low libido/sex drive despite getting morning erections.
In his own words

Pro Forma Analysis

I am going to do the same process as with the other Long COVID person. First, we have two lists of bacteria available, the number of studies are few but slowly increasing.

Bacteria Out of Range

The earlier sample had just 7 out of range, the latest sample increased to 16, implying the microbiome is drifting further away from normal. Comparing samples, we found the following concerningly high on both samples:

The following high level taxonomy items went out of range in the latest sample:

End Product Out of Range

Three items were out of range, one in common with the other Long COVID but in the opposite direction a-Galactosidase was high, and the other was low.

KEGG Bacteria Products Out of Range

The earlier sample had 9 out of range, the latest sample has 145!! Another indication of shifting further away from normal 🙁

KEGG Modules Out of Range

Just one in each sample, nothing in common.

KEGG Enzymes Out of Range

The earlier sample had 8 out of range, the latest sample has 139!! Another indication of shifting further away from normal 🙁

Kegg Suggestions

Where there are so many items with issues, I usually do not bother looking at them individually. Instead, I look at what can be computed to address them. Because every item is low, we do not need to look at trying to reduce anything — just add,

KEGG Suggested Probiotics

This is done by seeking out probiotic bacteria producing enzymes etc that are not being produced enough by existing bacteria. These can be viewed as a biological supplement producing items not available as regular supplements. The retail probiotics Sun Wave Pharma/Bio Sun Instant and Prescription Assist appear to be good choices (if available).

These are the same ones as with the other Long COVID person. What surprised me was that the earlier sample had a higher value list than the latest sample. This implies that the new overgrowth are providing the material to stablize the microbiome (unfortunately, in the current state of dysfunction)

A common mistake is to slip into a homeopathic thinking, “oh, I am taking some — that is enough”. In general I recommend starting low and increasing to the maximum dosages used in clinical studies. See this page for amounts used and links to the study or clinical trial.

KEGG Suggested Supplements

I tossed in the prior review for reference, two supplements are in common with all three samples.

Earlier Sample	Latest Sample	Other Person
beta-alanine iron L-Cysteine L-glutamine L-Lysine L-Proline Molybdenum NADH Vitamin B-12	beta-alanine Glycine L-asparagine L-Cysteine L-Lysine L-Proline L-Threonine L-Tyrosine Phytase (Enzyme)	beta-alanine D-Ribose iron L-Histidine L-Lysine L-Phenylalanine L-Tryptophan magnesium

We similarly identify supplements that are available retail (defined as being available on Amazon.com)

Suggestions

Using the last Long COVID post as a model, I jump directly to suggestions using the latest results. EXCEPT – I selected everything — including antibiotics and antivirals. No antibiotic made it high on either list.

12%ile and COVID-19

Remember, we are restricting to only those reported for active COVID and with the same direction of shift

12%ile and Long COVID

We have a much longer list of bacteria selected — which likely reflect that it is long COVID.

Quick Kaltoft-Moldrup suggestions

A very short list – this happen because we do not have studies reporting what modifies many of these bacteria.

The earlier sample had just a half dozen bacteria picked. The latest had more

Earlier had only a few (not even 20 Add Suggectios)

Reminder – The WHY for suggestions

On the suggestion line, you may see a 📚. Clicking it will show the source of the recommendation and why. Remember the more positive impact (by number of studies reporting the same), the greater the confidence shown. It is the confidence that it will shift in the desired direction. It is not which works better.

Putting Suggestions Together

With much bigger lists of bacteria, we also run the risk of more complexity and contrary suggestions [for example, bifidobacterium longum bb536 (probiotics) was a take, but bifidobacterium longum (probiotics) was an avoid]. I find myself giving the 12%ile and Long COVID Suggestions the greatest credence. It has some interesting

What seems to be reoccurring – make sure you look up dosages where available. Start low and work up to the maximum dosages used in clinical trials (after consulting with your medical professional)

Human milk oligosaccharides (prebiotic, Holigos, Stachyose)
iron (a component of rare meat and high-protein diet)
glycyrrhizic acid (licorice)

I also expanded the list to 50 pro and con and notice the following items of interest

On Pro (take) List
- Ayurveda and similar Herbs
- The Antibiotics used by Jadin for treating ME/CFS
On Con (Avoid List)
- Probiotics
- Antibiotics
  - rifaximin (antibiotic)s

Probiotic Advice

My read of the data is to avoid all Lactobacillus and Bifidobacterium probiotics. You have above the median amounts of both of them 85%ile and 66%ile respectively – you do not need more, in fact, they likely contribute to the dysfunction! Miyarisan, Prescript Assist (or Equilibrium), aor / probiotic-3 and Sun Wave Pharma/Bio Sun Instant appears to be the best retail candidates for probiotics.

This is a MODEL not a PROTOCOL

This is directed to people reading this post and saying “I will do what is described”. What is the difference? A Protocol comes from clinical experience and is a defined set of actions that are repeated for each patient. A model is a theoretical way to generate candidate actions that may help. This is not a model for Long COVID patients, it is a model for one person’s microbiome. Every Long COVID patient will have a different microbiome and thus different candidate actions. You can see this by looking at the next post on Long COVID microbiome.

An analogy, Long COVID can be compared to a headache. There are at least 17 types of headaches. You may need to see a dentist (tooth issues), or take a antihistamine (allergy) or take oxygen or …. Details drives the treatment.

For information on suitable 16s Microbiome Providers.

To help illustrate this, I have put the bacteria targeted from each of them below. You will note a lot is in common.

This image has an empty alt attribute; its file name is image-63.png

This image has an empty alt attribute; its file name is image-60.png

Logical Treatment Options based on test results

Above you read about this user’s frustrations with the medical professionals. The root problem is that profession runs on encyclopedic knowledge (often photographic memory) that looks for a match and retrieves it as treatment. I term this as cook-book medicine. If there are no matches, then we typically see “deer in the headlights“, a deer with a MD.

Microbiome Prescription builds predictive modelling with a wide variety of suggestion options. Most of the options do not require a prescription, the user is in primary control. There is a full chain-of-evidence to the basis of the suggestions for people to review (yes, some people may need to upgrade their reading skills). The core facts are your microbiome.

Improvements can be objectively measured (instead of a vague “do you feel better”). Feeling better is important, but it should not be the sole criteria.

Questions and Answers

For many of these questions I went to the “See Impact..” with the specific sample.

Q: I’m currently on bovine Colostrum, is it ok to keep taking it?

A: Bovine Colostrum is not the database, the closest match is whey. It has no known impact – so you can assume it is safe.

Q: I’m eating boiled and cooled down potato every day as source of resistant starch. Is it ok?

A: Cooking an item with resistant starch can breakdown that starch. see Resistant Starch Content in Foods Commonly Consumed in the United States: A Narrative Review [2020]).
As above – potatoes– no known impact — so you can assume it is safe.
But : raw potato starch is a negative
Resistant starch is a NEGATIVE

Q: Is Mutaflor ok? Since my E coli appears low? I’m sorry if I’m not following I’m going through brain fog.

A: As above – no known impact — so you can assume it is safe.

Q: I see the suggestions recommend against inulin. However, I’ve recently included garlic, onion and ginger in my diet. Are they ok?

Garlic – mild negative
Onion – no known impact — so you can assume it is safe.
Ginger – no known impact — so you can assume it is safe.

Q: ThryveInside also says I have zero bacteria for absorbing Vitamin K2 and refers to Bacillus. Is it ok to take Bacillus Subtilis from Natto?

A: You may wish to contact ThryveInside to find out exactly how they computed this. I show that you are at the 56%ile for vitamin K production.

You may wish to be explicitly tested for Vitamin K by your medical professional
Vitamin K2 0 As above – no known impact — so you can assume it is safe.
Bacillus Subtilis – it is a definite avoid, Use Vitamin K2 supplements

Q: Which product do you recommend for HMOs? I found this on Amazon:https://www.amazon.com/Holigos%C2%AE-Restore-Functional-Disorders-Medical/dp/B0859DHVK2Is this the one you are referring to?

A: Yes, That is actually the product that was used in most of the studies cited.

Q: Which nuts is best for my case (pistachio, hazelnut, cashew, brazillian nut, etc.)? I’ve been eating walnuts and almonds for several months.

A: I checked the types that we have data for:

Peanuts – no known impact — so you can assume it is safe.
Walnuts – positive impact
Generic nuts – no known impact — so you can assume it is safe.

Q: My vitamin D turned out high-normal. My 25-hydroxy vitamin D reading is 29.1 ng/ml & reference range (20 – 40). The suggestions included Vitamin D.

A: Vitamin D supplement are estimated to be a net negative benefit (same numbers as above). I looked at the citations used to make that decision and see a mixed impact on different items according to different studies. The results illustrates why suggestions may change from month to month. If new studies are added (which happens monthly) then the impact estimates change. My goal is deliver the best estimate from current studies – a moving target,

Whatever happens, I just want you to know that you have helped me a lot even before getting Covid-19… One word, thank you Ken 💐

REMINDER: These are suggestions generated by an artificial intelligence program. Before implementing, they should be reviewed by your medical professional.

Long Covid Patient Microbiome Analysis

One study suggests that a core microbiota could predict COVID-19 severity in healthy subjects.^²⁷ Another study shows that the composition of the intestinal microbiota in the Chinese cohort is different between COVID-19 infected and un-infected controls, with symptom severity correlating with specific bacterial taxa.^²
The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort [2021]

positive detection of SARS-COV-2 RNA from the respiratory tract, defined as respiratory positive (RP)
failure to detect in the respiratory tract, but had covid, is negative

Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study [2021]

Our Long COVID Patient

Their summary:

End of March 2020: covid
Tachycardia until July 2020.
MRI showed pericarditis.Tachycardia stopped once I resumed H1 blockers
- I had stopped out of paranoia when acutely ill, and B started antacid prescribed by cardiologist.
Severe constipation started at around April 2020. So we’re talking about over a year ago.
I had a break from constipation issue for about 6 months – november 2020 to may 2021.
Other ongoing symptoms are pain on the left side under the ribcage and internal vibrations, numbing of sensation “down there” (don’t feel much the need to go to the toilet,
Sex life is hampered too, nerve damage very likely according to myself and also gynecologist who thinks it’s postviral).
The entire first half of 2021 i adopted a diet based on green smoothies.
- Other than 80% veg based smoothies and flaxseed i ate some veg stir fries and fresh salmon and some crisps (in small quantities!!! but every day a little pack).
- Before covid i ate only crap, all sort of crap, so that this diet was for me a huge sacrifice.
- But since covid junk food made me feel bad anyway, so slowly i accepted to change my diet.
- I’m also taking a very long list of supplements. I had high cholesterol before covid, had it at 18 already despite being slim, but after covid it remained high and my sugar level got very high (not yet in the red). [This may no longer be true — the measurements were from a year ago]

Pro Forma Analysis

First, we have two lists of bacteria available, the number of studies are few but slowly increasing.

Bacteria Out of Range

I see 34 Outliers using the Kaltoft-Moldrup ranges (which are usually bigger ranges than most testing labs use). This person mentions 50+ out of range from their lab. Well, that huge number is precisely what the study above reported. This is not a typical microbiome disruption.

End Product Out of Range

Three items were LOW out of range, Vitamin D, Phosphoamidase, and a-Galactosidase. For Vitamin D we have the following literature:

Relevance of vitamin D ₃ in COVID-19 infection [2021] in which we find:
- “About 30% of COVID-19 patients also presented with cardiomyopathy (^{Arentz et al., 2020}). 1α,25(OH)₂D₃ plays a crucial role in the prevention of cholesterol build-up in the arteries by preventing the conversion of macrophages to foam cells (^{Oh et al., 2009}) and enhancing the cholesterol efflux from blood vessels (^{Yin et al., 2015})”
- She has cholesterol build up and a form of cardiomyopathy (See What About Tachycardia-induced Cardiomyopathy?) So low Vitamin D, the literature and her lab results are in agreement. This suggest serious Vitamin D3 supplementation (see Clinical Therapeutic Dosages here, I would suggest at least 10,000 IU/day — to be discussed with her physician)

KEGG Bacteria Products Out of Range

Every single one of a list of 47 was low. Not enough being produced

KEGG Modules Out of Range

Nothing reported

KEGG Enzymes Out of Range

As above, a list of 48 items with every item being low

Kegg Suggestions

KEGG Suggested Probiotics

This is done by seeking out probiotic bacteria producing enzymes etc that are not being produced enough by existing bacteria. These can be viewed as a biological supplement producing items not available as regular supplements. The retail probiotics Sun Wave Pharma/Bio Sun Instant and Prescript Assist appear to be good choices (if available). The fall back by species are:

KEGG Suggested Supplements

We similarly identify supplements that are available retail (defined as being available on Amazon.com)

beta-alanine
D-Ribose
iron
L-Histidine
L-Lysine
L-Phenylalanine
L-Tryptophan
magnesium

Suggestions

One unique feature of Microbiome Prescription is that it not only identifies candidate issue areas, it also makes suggestions based solely on studies from the US National Library of Medicine. These suggests factor in side-effects on other bacteria. Every other site, has a blinkered thinking with their suggestions and do not consider side effects. Of course, there is one layer of side effects that only your MD can help — medical conditions you have. A suggestion may suggest peanut butter and you have an allergy to peanuts!

Checking against COVID and LONG COVID Profiles

The studies report on the US National Library of Medicine and are coded for averages being statistically high higher or lower than controls. This does not mean that the values are extremes. Statistically, this presents some challenges. I decided to explore how many matches happened with different definitions (Kaltoft-Moldrup ranges, top/bottom 3,6,9,12,15 %ile) for COVID and LONG COVID

Process

For those who wish to do it themselves, go to advance suggestions and do settings like below.

We will be change Bacteria Slection and Explicit Bacteria

Then click the suggestions at the bottom. On the suggestion page, click Bacteria Details to see the bacteria that are picked

The results are below by bacteria. As we reduce how extreme values that are needed to be deemed “high” or “low”, we have more and more matches. C – active COVID; L – Long Haul COVID / Post COVID

Bacteria	KM	3	6	9	12	15
Anaerostipes	C / L	C/L	C/L	C/L	C/L	C/L
Peptostreptococcaceae	C / L	C/L	C/L	C/L	C/L	C/L
Acidobacteriia			C	C	C	C
Carnobacteriaceae			C	C	C	C
Finegoldia			C	C	C	C
Lachnospiraceae			C	C	C	C
Proteobacteria			C/L	C/L	C/L	C/L
Veillonella			C	C	C	C
Actinobacteria				C/L	C/L	C/L
Actinomyces				C	C	C
Mycoplasmataceae					C	C
Staphylococcaceae					C	C
Streptococcus					C/L	C/L
Campylobacter						C
Escherichia						C
Rothia						C
Tissierellales	L	L	L	L	L	L
Clostridiaceae	L	L	L	L	L	L
Bifidobacteriaceae			L	L	L	L
Bifidobacteriales			L	L	L	L
Bifidobacterium			L	L	L	L
Gammaproteobacteria			L	L	L	L
Negativicutes			L	L	L	L
Pediococcus			L	L	L	L
Turicibacter			L	L	L	L
Veillonellaceae			L	L	L	L
Bacilli				L	L	L
Roseburia				L	L	L
Streptococcaceae				L	L	L
Parabacteroides				L	L	L
Enterococcaceae				L	L	L
Enterococcus				L	L	L
Paraprevotella					L	L
Prevotella					L	L
Tannerellaceae					L	L
Collinsella						L
Coprococcus						L
Coriobacteriia						L
Lactobacillales						L
Odoribacter						L
Prevotellaceae						L

C – active COVID, L – Long COVID (i.e. 30+days after infection)

Suggestions – 3 approaches

After viewing the table above, I decided to do 3 approaches:

12%ile and COVID-19
12%ile and Long COVID
Quick Kaltoft-Moldrup suggestions

I expect all to be similar but with some differences. I will cut off suggestions around .425 to prevent information overload (which happens easily with the microbiome)

12%ile and COVID-19

The lack of a fine graduation of Confidence implies that we do not have that many applicable studies for the bacteria identified as important. Also this is what they had, not currently have.

12%ile and Long COVID

This has the graduation of Confidence values that I like to see.

Quick Kaltoft-Moldrup suggestions

Reminder – The WHY for suggestions

Putting Suggestions together

Remember that the purpose of the site is to create prescriptions — suggestions to correct microbiome shifts. The suggestions attempt to be adjusted for side-effects on other bacteria. Labs suggestions are based on blinkered analysis, “You are too high in X, Z reduces X so we recommend it” – which often ignores the fact that X also increases Y which is also too high.

Suggestions are computed in two different ways with no overlap of source data (KEGG based on genes, and studies where substances were tested). Items that are on both sets of recommendations are definitely things to consider. There are items that may be only on KEGG suggestions because no one has done studies on them.

So our very top suggestions are:

Probiotics
- clostridium butyricum (probiotics) see 📏 for dosages
- bifidobacterium longum (probiotics) see 📏 for dosages
Supplements
- vitamin d see 📏 for dosages

Go to https://microbiomeprescription.com/Library/Dosages , then search for the probiotic of interest. then click on 📏 Studies and Trials beside it to see the dosages

A second criteria is to eliminate any items where there are contradictions (“playing it safe), the following are my top suggestions

beta-alanine
iron
L-Histidine
L-Lysine
L-Phenylalanine
L-Tryptophan
magnesium
inulin (prebiotic)
fructo-oligosaccharides (prebiotic)
arabinoxylan oligosaccharides (prebiotic)
soy

At this point I should mention that a lot of items often used for microbiome issues appear contraindicated (i.e. AVOID). For example: neem, quercetin,resveratrol, triphala, resveratrol (grape seed/polyphenols/red wine), glycyrrhizic acid (licorice), melatonin supplement.

Remember, you can get opinions on over 3000 items in our database by going to the bottom of this list:

Iron was suggested by KEGG. I wanted to check it’s impact using the data from studies and was pleased with the result.

Iron was suggested by KEGG and appears to have a beneficial impact using studies data

I also confirmed magnesium was also a positive (and magnesium deficient, a negative)

This is a MODEL not a PROTOCOL

For information on suitable 16s Microbiome Providers.

Bottom Line

Another post COVID person just contacted me, with their samples, so a second COVID post is also available Both this person’s sample, and the recent study confirmed my suspicion that Long COVID is a Post-Infection Syndrome. Post-Infection Syndromes are, IMHO, infection altered microbiomes that failed to return to normal.

Dialog Notes with User

Q: “I’ve got a huge issue/reservation with a part of the concept: the norm in the distribution of the data base might be far from normal. And even further, what is normal might not be optimal at all. What is normal reflects an average diet, but maybe an optimal diet would lead to an outlier sample, how do you address that issue….”

A: I do not use a bell curve, See this post for where I have evolved to. It’s based on Percentile and shape of distributions

Q: As a laywoman looking at the data my immediate focus went to methane-sibo. This matches my current issues and I’m surprised you didn’t mention it.

A: SIBO does not have a microbiome signature that is reliable. See this 2017 post reviewing the literature on SIBO

REMINDER: These are suggestions generated by an artificial intelligence program. Before implementing, they should be reviewed by your medical professional.