This is a repost with expansion of “What is the best diet in your opinion?” on my CFS Remission blog back in 2018. It consists of the following

• Basic Logic for this diet
• How diets have changed in recent years — today’s “normal diet” is radically different than your recent ancestors
• The manifestation of “keeping up with the Jones” eating habits
• Finding Your Historic Diet – my own exploration

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I have been asked this often. My answer is extremely logical but not what you will get from most health experts (and unfortunately, may not be easy to determine for some, see “mutts” below). It is based on actual science and not idealogy.

The Diet…. it’s Logic

Very simple — the type of diet that your ancestors ate 300+ years ago! Diet changes gene expression, i.e. microbiome AND DNA adapts.

Last year, researchers discovered that these kinds of environmental genetic changes can be passed down for a whopping 14 generations in an animal – the largest span ever observed in a creature, in this case being a dynasty of C. elegans nematodes (roundworms)…. Usually, environmental changes to genetic expression only last a few generations.
…  studies have shown that both the children and grandchildren of women who survived the Dutch famine of 1944-45 were found to have increased glucose intolerance in adulthood.Scientists Have Observed Epigenetic Memories Being Passed Down For 14 Generations

What is 14 human generations? 300 to 420 years.

Maternal undernutrition during pregnancy (F(0)) programs reduced birth weight, IGT, and obesity in both first- and second-generation offspring. Sex-specific transmission of phenotypes implicates complex mechanisms including alterations in the maternal metabolic environment (transmaternal inheritance of obesity), gene expression mediated by developmental and epigenetic pathways (transpaternal inheritance of LBW), or both (IGT)

Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice [2009]

” Thus, it is possible to construct a chain of events, based on experimentally verified biochemical mechanisms, through which an environmentally induced change in the activity of chromatin-modifying enzymes can lead to a change in DNA sequence.”

Epigenetic responses to environmental change and their evolutionary implications [2009]

A diet based on typical diet of your ancestors 400 – 1400 years ago is likely a better choice than any healthy diet pitched by most people. Your gut bacteria is likely closer to the optimized bacteria your ancestors evolved from eating the same food for a thousand years.

Risk of introducing atypical foods

A new atypical food will have some bacteria/body tolerate it. For others, it may throw the body’s balance off; leading to autoimmune disease, diabetes, gluten sensitivity, autism, ADSD and a host of other conditions that appear to be increasing in western population ‘for no apparent cause’ (… cough, cough, cough). It’s a gamble for you and for your children. Yes, people will adapt and survive — but your offspring may not.

You should avoid the newly introduced foods (for your regions) that were not in use a couple of hundred years ago, for example, potatoes, peanuts (1920’s), and banana (which has been reduced to a single species, Cavendish – because it was the most profitable). The charts below show some of the abnormalities of diet seen recently. You also avoid process foods and modern additives (especially emulsifiers and new preservatives).

Some Drastic Changes seen in Diet

We can see that Americans have DOUBLED their meat consumption with almost a 10 fold increase of “healthy” chicken.

• ” In conclusion, consumption of lean red meat (lamb) or lean white meat (chicken) as part of the usual diet is associated with a similar lipid response.” [2011]
• “Consumption of lean red meat (Pirenaica breed) or lean white meat (chicken) as part of the usual diet is associated with a similar response. ” [2022]
• “There was no difference in BMI or any other marker of adiposity between consumption of pork, beef and chicken diets. ” [2014]

There are implication that this increase of meat may be a factor in increasing ADHD, Autism rates and autoimmune conditions:

• Maternal Western-style diet reduces social engagement and increases idiosyncratic behavior in Japanese macaque offspring [2022]
• The Influence of Maternal Metabolic State and Nutrition on Offspring Neurobehavioral Development: A Focus on Preclinical Models [2022]
• “Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic-pituitary-adrenal (HPA) axis.” [2015]

Sugar is added to almost all prepared foods. The reason is simple, it encourages consumption and thus more sales.

And we are eliminating other very tradition foods from our diet, for example legumes and dry beans.

legume consumption remained low in US adults and declined from 2011 to 2014 (mature legumes: 12.8 to 8.3%; dry beans: 10.0 to 6.5%).

Legume Consumption Patterns in US Adults: National Health and Nutrition Examination Survey (NHANES) 2011–2014 and Beans, Lentils, Peas (BLP) 2017 Survey [2020]

Keeping up with the Jones [Health Issues]!

My daughter has seen this in Vancouver, Canada – where almost 50% of the people were born outside of Canada.

Having grown up around such a large amount of immigration, the changes have been really apparent. Interestingly enough, those from India and area tend to keep the traditions at home for eating, so they don’t have such a big impact on their bodies. But those from Asia, they all essentially know that when they come to North America, they are going to gain a lot of weight. Whether it’s food culture or additives in food, it’s a big struggle. They tend to also have problems with both dairy and alcohol. 

Daughter

Keeping up with the Jones often include eating upscale for your own culture group or the population that you are residing in. A food that was once a special occasion food becomes a regular food as a statement of prosperity (and possibly stupidity!)

• Following the Indian Immigrant: adoption of westernization results in a western gut microbiome and an increased risk of inflammatory bowel diseases [2022]
• A Pilot Study of the Gut Microbiota Associated With Depressive Symptoms and Sleep Disturbance Among Chinese and Korean Immigrants in the United States [2022]
• “results showed that altitude was the most important factor affecting the variation in the microbial community” Succession of the Gut Microbiome in the Tibetan Population of Minjiang River Basin [2022]
• “Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation.” Microbial co-occurrence complicates associations of gut microbiome with US immigration, dietary intake and obesity[2021]
• The Impact of Migration on the Gut Metagenome of South Asian Canadians. [2021]
• The Impact of Childhood Growth Stunting and Post-Migration Dysbiosis on the Development of Metabolic Syndrome Among Indigenous Immigrant Mexican Women. [2020]
• Linking the westernised oropharyngeal microbiome to the immune response in Chinese immigrants. [2020]
• US nativity and dietary acculturation impact the gut microbiome in a diverse US population. [2020]
• Western oropharyngeal and gut microbial profiles are associated with allergic conditions in Chinese immigrant children.[2019]
  

Evidence of significant impact

• “Adherence to the ‘ethnic breads, legumes and nuts’ and ‘whole grains, fruit and dairy’ patterns was associated with a lower predicted cardiovascular diseases risk, and an inverse association for the ‘processed food and sugar-sweetened beverages’ pattern in an Asian population. ” [2022]
• “participants in the highest quintile of the refined-foods pattern had a greater risk of elevated 10-y cardiovascular diseases risk” [2016]
• “Patterns emphasizing higher consumption of vegetables, legumes, fruit, nuts, whole grains, fish, lean meat or poultry, … were generally associated with decreased risk of all-cause mortality. “
• Consumption of added sugars has been associated with increased risk of obesity [23,24,25] as well as increased risk factors for cardiovascular disease (CVD) [26], including dyslipidemia [27,28], elevated blood pressure [20,29,30], diabetes [21,31,32], non-alcoholic fatty liver disease [33,34], and even cognitive decline [35] and cancer [36,37].” [2016]
• “An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased Alzheimer’s disease  risk  [2022]

Finding Your Historic Diet – my own exploration

From a post that I did seven years ago [2015], I am using myself as an example — you will likely need to do your own research. Beware of revisionist view of traditional diets — research!

Some nuggets that I found in a Christmas Present…

My wife gave me “Danish Cookbooks” by Carol Gold. This is NOT a cook book, but rather an academic study of cookbooks published in Denmark.  I’m 100% Danish and very interested in history.

I have always been inclined towards going for ancestral diet patterns, and did Paleo for a while. My problem with Paleo is that it is more ideological based than actual (scientific-evidence) archeologically based. It is also trying to jump the diet back thousands of years which effectively ignores how our bacteria evolved to meet our changes of diet.

In this book, I found two gems from the historical records:

• We have decreased the use of spice considerably — in 1600, the common spices were:
  • cumin, anise, coriander, dill, fennel, lavender, sage, rosemary, mint, bay leaves, cloves, pepper, saffron, thyme, marjoram, nutmeg, cardamon, ginger, cinnamon, hyssop, wormwood, lemon balm, angelica-root.
  • “The issue here is … the use of seasonings in general slackens” p.47
  • Many of these spices (like wormwood and ginger) have strong antibacterial characteristics which would have kept some gut bacteria families in control well.
• “Their most common food was meat” p. 122
• White (wheat) bread was very uncommon, expensive, and typically seen only in upper class homes on special occasions(not as part of the regular menus) —Note this is in Northern Europe. It appears that most of the carbohydrates came from Rye Bread.

I am sure that some readers who favor a diet that is vegan or vegetarian on ideological grounds would object to these suggestions.  My response is simple, if your ancestors were vegetarians for centuries or millenniums (as some friends who were born in India can validly claim), then that is the right diet without any doubts.

Evidence shows that gut bacteria is inherited through generations — hence it is good to know what your ancestors ate because your gut bacteria have likely adapted to that diet. Given my heritage (which likely applies to people from the UK, Poland, northern France and Germany etc), this boils down to:

• Rye Bread without any wheat flour
• Meat and Fish (especially since the family seemed to always been within 5 miles of the coast back to 1500..)
• Often goat milk and goat cheese (Gjetost) were the norm and not cow milk.
• Vegetables:
  • Cauliflower
  • Artichoke
  • Rutabaga
  • Turnip
  • Beets “From the Middle Ages, beetroot was used as a treatment for a variety of conditions, especially illnesses relating to digestion and the blood.”
  • For more, see http://www.oldcook.com/en/medieval-vegetables

No potatoes — they really did not enter my ancestor dies until the early 1800’s – after one of my great-grandfathers was born. Little or no sugar (“Worldwide through the end of the medieval period, sugar was very expensive^[1] and was considered a “fine spice“,^[2] but from about the year 1500, technological improvements and New World sources began turning it into a much cheaper bulk commodity.” – Wikipedia)

Dropping back earlier in my ancestry, the Vikings. We have an excellent summary here “Viking Diet: Why you should eat like the Vikings did!” which cites historic text describing the food with archeological findings.
“Vikings farmed cold-hardy vegetables like cabbage, carrots, leeks, turnips, parsnips, garlic, onions, and other root vegetables to add vitamins and variety to their diets. They ate peas, beans, and other legumes. They were fond of apples and cherries from wild or cultivated trees and collected berries and nuts when they were in season.“

There is an excellent interview with a specialist: Nordic food culture – A historical perspective by Henry Notake. He cites “the practice of soaking fish in lye is not an original Norwegian tradition, even though the actual raw material of dry fish is. I have found recipes for lutefisk in German cookbooks, Swedish documents from the 16th century, and Spanish and Polish cookbooks from the 17th century. ” He is also the author of Printed Cookbooks in Europe, 1470-1700

Frumenty for Breakfast?

Some foods that are common now were not the case in the past and vice versa.

A Dollop of History, describes this and how to make it. It used  Furmente wt Porpays (Frumenty with Porpoise) from the 14th century English manuscript, The Forme of Cury. This food and similar recipes dates back to Roman Times. It uses saffron. If you can’t get porpoise, oogruk (bearded seal) is a good substitute (a unique taste according to my wife from her own experience). For other recipes see: Medieval Recipes and Ancient Recipes on the same site.

One item to keep in mind, often surviving recipe books were written to the upper class and not your ancestors! Many recipes on the internet are modern adaptions of old recipes to suit contemporary tastes — so be warned!

Project Gutenberg does have some historic cook books available (besides The Forme of Cury cited above)

• The accomplisht cook [1588] by Robert May
• The Queen-like Closet or Rich Cabinet [1670] Hannah Woolley
• English Housewifry [1752] by Elizabeth Moxon

A list of 13-16th century cook books is on Old Cook with a list of recipes in English. Compare to this, a modern omelet is rather plain!

Ingredients (1 tsp = 1 teaspoon)
6 leaves of tansy
1 rue leaf
4 leaves of Apium (wild celery)
4 mint leaves
4 sage leaves
6 leaves of marjoram or oregano
handful of fennel (aromatic foliage)
large handful of parsley
2 handfuls of the mixture: violet leaves, spinach, lettuce, green chard
16 eggs
1tsp of ginger
salt.

Omelette with herbs, from Arboulaste , Ménagier de Paris, 1393.

This Wikipedia article may be a helpful start for many.

The last item needs to be taken with a touch of salt and sung: “A spoonful of soil helps the microbiome recover!” We have become hyper-hygienic. See the Hygiene hypothesis. This comes from a post in 2016:

“The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices….Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish” – i.e. industrialized farming practices resulted in six times (600%) the rate of asthma and allergies. See Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children(2016). This is also echoed in their farm products!!! Amish and Hutterite Environmental Farm Products Have Opposite Effects on Experimental Models of Asthma [2016]. Given a choice of buying groceries from a Hutterite farm or a Amish farm, buy the Amish (non industrialized) groceries!!!!

So I advocate not a Paleo diet, but a regional medieval-food diet (partially modified for modern nutritional needs). No prepared foods (talk about being extremely unnatural!), so food prepared from scratch — ideally organic with heritage seeds. Orange carrots are unnatural! Carrots should be white! The food should also be seasonal! The rotation of food with the seasons is a significant factor. Having fresh strawberries at Christmas is so very wrong.

Are you a Mutt?

The term mutt or “Heinz 57″means mixed ancestry – for example, Asian with African, Icelander with Italian. If you are not sure, a DNA test is suggested.

If you are a mutt, look for commonality of historic foods from the dominant ancestors.

Are what you have been told is healthy wrong?

Chances are that it is corrected relative to the typical common western diet. That is the base line that most studies are done against. If you change the base line, the answer may change…

One other factor?

There is evidence that a combination of blood type and being a secretor  or non-secretor impacts the body and the microbiome. There is a nice blood type table by country listed here. Iceland and Ireland are very similar (partially because both had major Viking settlements 1200 years ago). One could propose a model that traditional regional diet influenced the survival rate of different blood type which would be reflected in their blood type distribution. Compare the Scandinavian (meat eaters) to India/Sri Lanka (Vegetarians) below for aNeg,bPos and oNeg.

country	oPos	aPos	bPos	abPos	oNeg	aNeg	bNeg	abNeg
Denmark	35	37	8	4	6	7	2	1
Norway	33.2	41.6	6.8	3.4	5	7.4	1.2	0.6
Sweden	32	37	10	5	6	7	2	1
Iceland	46.8	27.2	9	2	8	4.8	1.6	0.4
Sri Lanka	43.42	21	25.78	5.13	2	1.04	1.25	0.26
India	32.53	21.8	32.1	7.7	2	1.36	2	0.48
United Kingdom	44	28	8	2	9	6	2	1
United States	37.4	35.7	8.5	3.4	6	6.3	1.5	0.6
Ireland	47	26	9	2	8	5	2	1

Bottom Line

Showing off prosperity by what you eat, trying to assimilate into local or trendy eating habits and convenient “get-healthy” diets are excellent ways to cripple your microbiome (and likely future generations). One simple example is going gluten-free. For some medical conditions it is necessary — but for a person without those conditions, available studies suggests that it is a poor choice advocated by naïve people

• ” Gluten-Free Diet Reduces Diet Quality and Increases Inflammatory Potential in Non-Celiac Healthy Women” [2022]

Food taste is acquired — cutting sugar and salt from the diet can be hard for many people. Eating turnips and rutabaga may be unfamiliar tastes. Eating 100% rye bread with goat cheese is definitely a different taste. It will take time and may present extra challenges if you have kids or other in the family that want to stick to contemporary eating habits.

My daughter states “There’s a reason why old recipes don’t always work, because ingredients are either no longer available, or they have changed over the years, or techniques have changed (see this post)”

So that is my logic and my reasoning and my evidence…

Comments from Social Media

Using my last post, The root of all evil in the Microbiome?, I tried identifying items that address many of the evils. The process is simple, I use Microbiome Prescription existing database with 2,099.126 interactions between gut modifiers and bacteria. I then select items that only increase the top N items. Starting with 2 items and then working up.

Two Items: Prevotella, Veillonella

Produced following items

• Amino Acid and similar
  • acetic acid
  • l-citrulline
    • propionate
• Antibiotics, Antivirals etc
  • rifaximin (antibiotic)s
• Diet Style
  • ketogenic diet
• Food (excluding seasonings)
  • blackcurrant
  • cranberry bean flour
  • Far infrared Sauna
  • fasting
  • lupin seeds (anaphylaxis risk, toxic if not prepared properly)
  • Miso
  • pea (fiber, protein)
  • Pulses
  • red wine
  • wheat bran
• Herb or Spice
  • Bofutsushosan
  • chinensis (Chinese goldthread)
  • isobutyric acid
  • isovaleric acid(fatty acid)
  • smoking
• Prebiotics and similar
  • arabinoxylan oligosaccharides (prebiotic)
  • galacto-oligosaccharides (prebiotic)
  • xylan (prebiotic)
• Probiotics
  • Lentilactobacillus buchneri
• Sugar and similar
  • non-starch polysaccharides
  • saccharin
• Vitamins, Minerals and similar
  • vitamin d

Three Items: Prevotella, Veillonella, Clostridium

We are done to just one item: Amino Acid and similar l-citrulline

This is not unexpected, in building the suggestions algorithms, I often encountering items that helps one and hurts another; also a lack of studies.

Alternative Approach

I am going to pick the top dozen (12) genus, and then select the items by the number of genus positively impacted. As you see, the best that we get is impacting 50% of the genus picked.

Remember: we are doing items with absolutely positive impact only. We exclude all items that has a negative impact on any of the genus reported in any study. For clarity, if a substance increases a genus in some studies and decreases in other studies, it is excluded. This is the most conservative approach.

Caution: this assumes undergrowth for all 12 genus. It may make an overgrowth worse.

ModifierType	Modifier2	Cnt
Prescription – Other	proton-pump inhibitors (prescription)	6
Sugar and similar	non-starch polysaccharides	5
Amino Acid and similar	acetic acid	3
Amino Acid and similar	Conjugated Linoleic Acid	3
Amino Acid and similar	l-citrulline	3
Amino Acid and similar	proline (amino acid)	3
Diet Style	animal-based diet	3
Food (excluding seasonings)	blackcurrant	3
Food (excluding seasonings)	fasting	3
Food (excluding seasonings)	lupin seeds (anaphylaxis risk, toxic if not prepared properly)	3
Food (excluding seasonings)	Pulses	3
Food (excluding seasonings)	safflower oil	3
Food (excluding seasonings)	wheat bran	3
Miscellaneous, food additives, and other odd items	isobutyric acid	3
Miscellaneous, food additives, and other odd items	isovaleric acid(fatty acid)	3
Prebiotics and similar	arabinoxylan oligosaccharides (prebiotic)	3
Sugar and similar	saccharin	3
Amino Acid and similar	propionate	2
Diet Style	fibre-rich macrobiotic ma-pi 2 diet	2
Food (excluding seasonings)	barley,oat	2
Food (excluding seasonings)	cranberry bean flour	2
Food (excluding seasonings)	Miso	2
Food (excluding seasonings)	navy bean	2
Food (excluding seasonings)	pectin	2
Food (excluding seasonings)	red alga Laurencia tristicha	2
Herb or Spice	Bofutsushosan	2
Herb or Spice	coptis chinensis (Chinese goldthread)	2
Herb or Spice	plantago asiatica l.	2
Herb or Spice	schisandra chinensis(magnolia berry or five-flavor-fruit)	2
Miscellaneous, food additives, and other odd items	Tributyrin	2
Prebiotics and similar	carboxymethyl cellulose (prebiotic)	2
Prebiotics and similar	oligofructose (prebiotic)	2
Prebiotics and similar	resistant maltodextrin	2
Prescription – Other	epicor	2
Probiotics	bacillus subtilis natto (probiotics)	2
Probiotics	saccharomyces boulardii (probiotics)	2
Sugar and similar	glucose (sugar)	2
Sugar and similar	levan	2
Vitamins, Minerals and similar	Ferric citrate	2

Bottom Line

The above is a generic list that should “do no harm” for most people and will likely help. Better results are likely to occur using a 16s microbiome report (OmbreLabs [US only] and Biomesight [World wide] are the most used) and using the Artificial Intelligence on Microbiome Prescription that factors in the 2 million facts that it has available (see this example). That would produce a targeted list for your needs.

From Special Studies, I extracted the genus who are associated with various symptoms/conditions and then aggregated into a single table below. See Special Studies Updated and A new specialized selection of suggestions links for background.
UPDATE: Just added Possible help for the root of all evil in the microbiome?

Conceptually, these are the ones that will lead to a variety of symptoms and conditions. Two of the more significant ones are available as probiotics:

• Clostridium (i.e. miyarisan (jp) / miyarisan)
• Bifidobacterium (many brands, I tend to favor Custom Probiotics offerings with HMO)
• Prevotella may be available as a retail probiotic soon (see Prevotella copri as Next Generation Probiotics). There is also a US Patent for  Prevotella histocola which implies work on producing it.
• Veillonella probiotics appear to be available in a mixture (ULTRA-VEILLONELLA) however, I have reservations about the seller (site is new – 2022, no species information, no safety or other studies (legally required in the USA), no information about the company, etc. in other words has an unpleasant smell)
• Note that Lactobacillus is far down this list.

CLICK ON THE BACTERIA BELOW TO SEE WHAT INCREASES OR DECREASES EACH

Bacteria Rank	Shifted	Conditions	Sum Of Conditions
Prevotella	Low	22	145
Veillonella	Low	21	113
Clostridium	Low	21	102
Bifidobacterium	Low	20	151
Anaerococcus	Low	17	79
Phocaeicola	Low	17	78
Streptococcus	Low	15	118
Bacteroides	Low	14	72
Peptoniphilus	Low	14	69
Blautia	Low	14	64
Lactobacillus	Low	14	51
Megasphaera	Low	13	51
Erysipelatoclostridium	Low	13	51
Schaalia	Low	13	42
Lactiplantibacillus	Low	13	39
Escherichia	Low	12	36
Porphyromonas	Low	11	46
Corynebacterium	Low	8	39
Fusobacterium	Low	8	31
Slackia	Low	8	27
Campylobacter	Low	7	23
Succinivibrio	Low	6	22
Collinsella	Low	6	22
Roseburia	Low	5	17
Actinobacillus	Low	5	17
Mediterraneibacter	Low	5	16
Megamonas	Low	5	15
Hungatella	Low	5	15
Catenibacterium	Low	4	20
Desulfovibrio	Low	4	19
Haemophilus	Low	4	18

With this being the Thanksgiving Weekend, I had time to work on my backlog. One of the items was special studies. I have done the following changes:

• Executed the analysis for both uBiome and Thryve/Ombre samples. So more samples will have the option of using special studies.
• Implemented Consensus/Monte Carlo between the bacteria, casting the species (which are not reported consistently between labs) to their genus. These are shown on the [Key Bacteria] link below.

Last, I have added per  Peripheral neuropathy to the symptom list.

REMEMBER TO ANNOTATED YOU SAMPLES WITH YOUR SYMPTOMS

This is what Special Studies use.

Example: for Chronic Fatigue Syndrome

The page below shows a distinct pattern for ME/CFS with Bifidobacterium being the greatest significance. For this bacteria, my first suggestion is simple:  Human milk oligosaccharides (HMOs) and Bifidobacerium infantis probiotics.

• Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology [2020]
• “The results reflect the metabolic abilities of the respective bifidobacteria. B. bifidum used secretory glycosidases to degrade HMOs, whereas B. longum subsp. infantis assimilated all HMOs by incorporating them in their intact forms.” [2011]

It is interesting to note that Lactobacillus does not appear as significant.

Bottom Line

Special Studies are still a “work-in-progress”. Using them “as is” have not produced superior results to those from the standard triplet (Outside Lab Range, Box-Plot-Whiskers, Kaltoft-Moldrup) — see this post for an example. How do I determine which is better? For ME/CFS, we should have the top suggested items being cross validated with clinical studies. Feel free to explore the results.

I will continue working on getting superior results from special studies — stay tune!

Back Story

I go this email from someone who just moved to Spain from the U.S. She has being using Microbiome Prescription to try improving her ME/CFS. She had the testing done by Ombre Labs, and then transfer the data to BiomeSight. This allows her to keep consistent analysis on her journey of recovery.

I’m doing pretty well with bacillus coagulans and pretty bad with some other recommendations so I’m looking for some extra clarity. When I hit a great herbal antibiotic and a great probiotic life gets so much better, but oftentimes it’s harder than that. Sometimes I don’t get enough  herbal antibiotic recommendations. Some of the probiotics I may need, like e-coli or bifidus, cannot sustain me the way coagulans does -keeping my local infections at bay. So I try to combine them  or if it’s not clear if they are compatible, I tend to not take them, which is a shame. So I’m considering prescription medicine to see if I can get a bit more help.

I’m also figuring out where to buy supplements etc. Life is really an adventure!

Comparison Between Samples And Lab Interpretations

For those not familiar with the issue of Lab Interpretation of the identical data see The taxonomy nightmare before Christmas…[2019]. Ombre typically reports on 25-30% more bacteria types than BiomeSight. The quality improved, but the number of bacteria identified are very similar. I give observations below:

	Ombre	Lab	Results	BiomeSight	Lab	Results
Criteria	6-Jul	19-Aug	10-Oct	6-Jul	19-Aug	10-Oct
Lab Read Quality	2.1	5.4	7.1	2.1	5.4	7.1
Bacteria Reported By Lab	365	628	625	280	497	490
Bacteria Over 99%ile	5	6	0	2	7	1
Bacteria Over 95%ile	27	24	1	19	31	11
Bacteria Over 90%ile	49	51	1	37	58	24
Bacteria Under 10%ile	18	60	485	45	62	224
Bacteria Under 5%ile	10	28	411	28	30	175
Bacteria Under 1%ile	1	7	317	1	13	135
Lab: Thryve
Rarely Seen 1%	0	9	1	0	4	2
Rarely Seen 5%	8	40	27	4	18	17
Pathogens	19	28	25	15	26	16
Outside Range from Medivere	16	16	5	4	4	4
Outside Range from Metagenomics	7	7	19	17	17	16
Outside Range from MyBioma	14	14	8	7	7	7
Outside Range from Nirvana/CosmosId	23	23	8	9	9	7
Outside Range from XenoGene	33	33	25	22	22	19
Outside Lab Range (+/- 1.96SD)	10	14	42	28	28	22
Outside Box-Plot-Whiskers	64	61	12	6	13	7
Outside Kaltoft-Moldrup	112	182	31	70	84	64
Condition Est. Over 99%ile	0	0	542	70	113	175
Condition Est. Over 95%ile	0	0	0	0	1	0
Condition Est. Over 90%ile	2	2	10	0	4	0
Enzymes Over 99%ile	13	15	17	0	6	0
Enzymes Over 95%ile	69	82	0	0	10	0
Enzymes Over 90%ile	155	411	0	22	32	0
Enzymes Under 10%ile	55	138	2	45	51	21
Enzymes Under 5%ile	22	67	1593	308	219	212
Enzymes Under 1%ile	5	2	1320	187	132	146
Compounds Over 99%ile	104	126	641	12	47	67
Compounds Over 95%ile	385	397	4	30	7	19
Compounds Over 90%ile	533	548	60	112	76	138
Compounds Under 10%ile	183	248	103	342	313	323
Compounds Under 5%ile	109	127	359	180	125	224
Compounds Under 1%ile	16	17	303	37	64	73
Compounds Under 1%ile	17	21	224	17	21	40

The following are apparent, between the last two samples, the reader was trying to follow the suggestions.

• The number of high bacteria (> 90%ile, > 95%ile, > 99%ile) show significant decline
• Rarely Seen bacteria show significant decline
• The number of low bacteria (< 10%ile, < 5%ile, < 1%ile) show significant increases – suggesting more diversity
• The Outside Range is a little mixed, with either both labs showing a decline, OR one showing a decline and one an increase. None showed increase on both.
• High Enzymes show decline. Low Enzymes had inconsistent results.
• Compounds and Conditions had inconsistent results

Enzymes, Compounds and Conditions are best effort estimates (and experimental) and be taken with a grain of salt (50 mg). By conventional thinking, the microbiome has improved (less extreme high levels), less pathogenic bacteria types.

Going Forward

Consensus approach (also known as Monte Carlo Simulation) remains the safest choice. To simplify the analysis, I will use the standard triplet (Outside Lab Range, Box-Plot-Whiskers, Kaltoft-Moldrup) on both latest samples processed through Ombre and Biomesight data processing. Given the report that some did not work subjectively, I decided to proceed down the most restrictive approach. I used the new quick suggestions (best choice for someone with brain fog).

Probiotics

The #1 and #2 choices are lactobacillus paracasei and bacillus subtilis. Kegg choices are Escherichia coli, Bacillus subtilis (with Biomesight numbers being much less than Ombres).

	Thryve			Biomesight
Microbiome Modifier	Suggestions	Clinical Dosage	Est Confidence	Suggestions	Est Confidence
bacillus subtilis	Take	10 BCFU/day	340.4	Take	223.6
bacillus lichenformis	Take		279.1	Take	20.9
enterococcus faecium	Take	1 BCFU/day	13.2	Take	8
bifidobacterium longum	Take	10 BCFU/day	516.2	Take	182.5
lactobacillus paracasei	Take	40 BCFU/day	58.7	Take	397.5
pediococcus acidilactici	Take		157.7	Take	215.4

For other items, there were a surprisingly few in agreement.

Microbiome Modifier	Suggestions	Clinical Dosage	Est Confidence	Suggestions	Clinical Dosage	Est Confidence
galactooligosaccharides (GOS)	Take	10 gm/day	15	Take	10 gm/day	139.1
Calcium	Take	500 mg/day	129.2	Take	500 mg/day	36.2
Magnesium	Take	500 mg/day	189.7	Take	500 mg/day	119.2
D-Ribose	Take	10 gm/day	80.6	Take	10 gm/day	23.6
Glycine	Take	15 gm/day	409.2	Take	15 gm/day	258.5
Omega-3 fatty acids	Take	4 gm/day	166.8	Take	4 gm/day	289.4

Using the Consensus across Multiple Samples

This gives a lot more information, but at the cost of more complexities.

The approach is similar to the above, except for suggestions we change to Every thing. I have extracted the items > 100 that are 5 or 6 Take Count with 0 or 1 Avoid Count to the table below in decreasing order

• Cacao (426) — not an item on the quick suggestions
  • High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome [2010]
• bifidobacterium longum (probiotics)
• glycine
• high resistant starch
• palm kernel meal (300 and below)
• almonds/ almond skins
• bacillus subtilis (probiotics)
• bifidobacterium pseudocatenulatum,(probiotics) (Stain versus is negative)
• high fiber diet
• brown algae
• omega-3 fatty acids (200 and below)
• pediococcus acidilactic (probiotic)
• oligofructose (prebiotic)
• lactobacillus paracasei (probiotics)
• brown rice
• Mangosteen
• whole-grain wheat
• magnesium
• navy bean
• bacillus licheniformis,(probiotics)
• green tea
• lactulose
• lauric acid(fatty acid in coconut oil,in palm kernel oil,)

Prescription Drugs Analysis

The approach is similar to the above, except for suggestions we change to Every thing.

And then use the option on the Multiple Samples tab,

Remember to empty the old baskets.

The items that came up (as discussed above) are:

• minocycline (antibiotic)s
  • Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage [2021]
  • Could Minocycline Be a “Magic Bullet” for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? [2021]
  • Improvement of chronic nonspecific symptoms by long-term minocycline treatment in Japanese patients with Coxiella burnetii infection considered to have post-Q fever fatigue syndrome [2004]
• proton-pump inhibitors (prescription)
• ceftriaxone (antibiotic)s (often give with azithromycin – which has been used for ME/CFS)
  • “A study by Fallon et al found that some of the PTLDS patients in their trial experienced moderate short-term cognitive improvement from ceftriaxone treatment” [2008]
  • “Ceftriaxone has excellent penetration of the blood-brain barrier and is one of the most effective drugs for Lyme disease. Ceftriaxone is typically given once a day intravenously, typically in 45 minutes.” [Columbia-Lyme.Org]
  • “Ceftriaxone Compared with Doxycycline for the Treatment of Acute Disseminated Lyme Disease [1997]
• rifaximin (antibiotic)s – often used for IBS that is co-morbid with ME/CFS
  • See this 2015 post, Rifaximin and CFS , for CFS/ME that have used this

So every item at the top of the list (from over a possible choice of 3000 different prescription drugs), are cross-validated against the literature with the exception of proton-pump-inhibitor. This person can show their medical professional that the microbiome model suggests it and clinical studies confirm that they are reasonable.

I favor Dr. Cecile Jadin protocol of rotating antibiotics typically a course (7-10 days), then a break of 1-2 weeks, and then proceed to the next one.

Feedback from Reader

I love Dr. AI [Artificial Intelligence], which other doctor asks you to eat as much 100% chocolate I can??? And I tolerate it, luckily. And there are so many yummy brands in Spain, I don’t remember having that much choice when I left! 

Thanks for all the info, very helpful, very encouraging to see progress “on paper”, and to have clear things to share with my new doctor. I’m confident I’ll find a microbiome helper here in Barcelona.

The greatest challenge in treating ME/CFS is that there is no clear test to see if something is helping. Using repeated microbiome samples with systematic trials of suggestions, provides objective evidence — even when the subjective evidence is not pronounced. ME/CFS patients have a real challenge on doing subjective evaluation — they often cannot recall how they were two weeks ago!

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

The answers above describe my logic and thinking and is not intended to give advice to this person or any one. Always review with your knowledgeable medical professional.

A reader asked to look at the data from an experiment she did.

I have provided two biomesight results from biomesight (BS) to microbiome prescription (MP). The sample consuming kefir daily was sent first (both to BS and MP). The second sample was after stopping kefir consumption between the two samples.

This was not the ideal sequence, getting a sample before doing Kefir and one after would be the typical approach. This approach should indicate what is lost by stopping. There was 3 weeks washout time before samples.

Analysis

The stopped Kefir sample is higher quality, so the expectation would be for the numbers to be higher. This is not the case. Stopping resulted in more extreme ranges for bacteria(1.5x more), less types of bacteria, dramatic drop in the count of bacteria out of range (93% decrease in Outside Lab Range). There was a significant in compounds being produced by the microbiome that were more extreme (8x increase) and enzymes also (3.6x increase).

Criteria	On Kefir	Stopped Kefir
Lab Read Quality	3.9	5.3
Bacteria Reported By Lab	470	404
Bacteria Over 99%ile	11	0
Bacteria Over 95%ile	30	5
Bacteria Over 90%ile	43	19
Bacteria Under 10%ile	10	74
Bacteria Under 5%ile	1	39
Bacteria Under 1%ile	0	7
Lab: BiomeSight
Rarely Seen 1%	2	2
Rarely Seen 5%	12	14
Pathogens	29	22
Outside Range from JasonH	4	4
Outside Range from Medivere	14	14
Outside Range from Metagenomics	7	7
Outside Range from MyBioma	5	5
Outside Range from Nirvana/CosmosId	19	19
Outside Range from XenoGene	21	21
Outside Lab Range (+/- 1.96SD)	18	1
Outside Box-Plot-Whiskers	73	29
Outside Kaltoft-Moldrup	81	74
Condition Est. Over 99%ile	0	0
Condition Est. Over 95%ile	0	0
Condition Est. Over 90%ile	1	1
Enzymes Over 99%ile	1	0
Enzymes Over 95%ile	3	2
Enzymes Over 90%ile	24	41
Enzymes Under 10%ile	79	240
Enzymes Under 5%ile	26	158
Enzymes Under 1%ile	1	47
Compounds Over 99%ile	0	2
Compounds Over 95%ile	4	113
Compounds Over 90%ile	29	453
Compounds Under 10%ile	44	163
Compounds Under 5%ile	18	61
Compounds Under 1%ile	2	8

As often happens, there is a Yin/Yang with some indicators improving and other worst. My general impression is that this microbiome does better on Kefir.

Bacteria Specifics

I then went to compare specific bacteria shifts that had special interest or large shifts

Bacteria	On Kefir Percentile (Percentage)	Stop Kefir Percentile (Percentage)
(genus) Bifidobacterium	35	72
(genus) Lactobacillus	none	43
(genus) Blautia	38 (6.5%)	46 (7.2%)
(genus) Faecalibacterium	34 (8.4%)	62 (14.6%)
(genus) Lachnospira	21 (0.6%)	70 (3.5%)
(genus) Bacteroides	66 (29.1%)	88 (40.5%)
(genus) Phocaeicola –	79 (15%)	93 (23%)

In terms of the literature, I could only find Bacteroides and Phocaeicola, which are both reported to increase (agrees). Different Kefirs will have different impact because each has different bacteria in it. “The kefir granules are a consortium of bacteria and yeasts embedded in a exopolysaccharide matrix. ” [2022]

See Milk kefir: composition, microbial cultures, biological activities, and related products [2015] for various lists of bacteria in different kefir tested.

List of Possible Bacteria in Kefir

The following list illustrates why I tend not to recommend Kefir — too many possible bacteria, some good and some bad. It’s probiotic roulette! If you buy commercial Kefir, have some fun — email the producer and ask which strains are in it, and the last full shotgun lab report verifying it.

1. Acetobacter acetic
2. Acetobacter fabarum
3. Acetobacter lovaniensis
4. Acetobacter orientalis
5. Acetobacter rancens
6. Acetobacter sp.
7. Acetobacter syzygii
8. Acinetobacter sp.
9. Bacillus sp.
10. Bacillus subtilis
11. Bifidobacterium bifidum
12. Bifidobacterium sp.
13. Brettanomyces sp.
14. Candida inconspicua
15. Candida krusei
16. Candida lambica
17. Candida maris
18. Candida sp.
19. Cryptococcus sp.
20. Dekkera anomala
21. Dysgonomonas sp.
22. Enterococcus durans
23. Enterococcus faecalis
24. Enterococcus sp.
25. Escherichia coli
26. Gluconobacter frateurii
27. Gluconobacter japonicus
28. Halococcus sp.
29. Kazachastania khefir
30. Kazachstania aerobia
31. Kazachstania exigua
32. Kazachstania unispora
33. Kluyveromyces lactis
34. Kluyveromyces marxianus
35. Kluyveromyces marxianus var. lactis
36. Lachancea meyersii
37. Lactobacillus acidophilus
38. Lactobacillus amylovorus
39. Lactobacillus brevis
40. Lactobacillus buchneri
41. Lactobacillus casei
42. Lactobacillus casei ssp. pseudoplantarum
43. Lactobacillus crispatus
44. Lactobacillus delbrueckii ssp. bulgaricus
45. Lactobacillus helveticus
46. Lactobacillus kefir
47. Lactobacillus kefiranofaciens
48. Lactobacillus kefiranofaciens ssp. kefiranofaciens
49. Lactobacillus kefiranofaciens ssp. kefirgranum
50. Lactobacillus kefiri
51. Lactobacillus lactis
52. Lactobacillus lactis ssp. lactis
53. Lactobacillus parabuchneri
54. Lactobacillus paracasei
55. Lactobacillus parakefir
56. Lactobacillus parakefiri
57. Lactobacillus plantarum
58. Lactobacillus satsumensis
59. Lactobacillus sp.
60. Lactobacillus uvarum
61. Lactococcus cremoris
62. Lactococcus lactis
63. Lactococcus lactis ssp. cremoris
64. Lactococcus lactis ssp. lactis
65. Lactococcus lactis ssp. lactis biovar diacetylactis
66. Lactococcus sp.
67. Leuconostoc lactis
68. Leuconostoc mesenteroides
69. Leuconostoc paramesenteroides
70. Leuconostoc pseudomesenteroides
71. Leuconostoc sp.
72. Naumovozyma sp.
73. Pelomonas sp.
74. Pichia guilliermondii
75. Pichia kudriavzevii
76. Pseudomonas sp.
77. Saccharomyces cerevisiae
78. Saccharomyces sp.
79. Saccharomyces turicensis
80. Saccharomyces unisporus
81. Saccharomycodes sp.
82. Shewanella sp.
83. Streptococcus durans
84. Streptococcus sp.
85. Streptococcus thermophilus
86. Weissella sp.
87. Zygosaccharomyces sp.

Comments from Social Media

There are two border walls that can be important to health, we will used these terms:

• increased intestinal permeability or IIP (often called Leaky Gut, but note: “Leaky gut syndrome is a hypothetical condition that’s not currently recognized as a medical diagnosis.”[src])
• blood–brain barrier permeability or BBBP

The first is an indicator of the availability of bacteria, fungi, chemicals, etc. to move from the intestines into the body/blood. The second is the ability of bacteria, fungi, chemicals, etc. to enter the brain. Both are important — the latter with neurological conditions (for example brain fog, autism, etc).

IIP – Increased Intestinal Permeability

This is usually associated with the Zonulin protein.

• Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer [2011]
• Zonulin, regulation of tight junctions, and autoimmune diseases [2012]

Zonulin is a protein modulator of intercellular tight junctions. It has been shown to induce a significant and reversible increase in gastroduodenal and small intestinal permeability and is involved in tolerance/immune response balance. The hybridization of wheat to dramatically increase gluten (gliadin) content and its overconsumption, multiple times a day, every day, in the typical diet, chronically disrupts this tolerance/immune response balance.

Michael T. Murray ND, John Nowicki ND, in Textbook of Natural Medicine (Fifth Edition), 2020

Zonulin is a member of the MASP (mannose‐binding lectin‐associated serine protease) family of proteins, and elevated serum zonulin levels have been reported in a number of neurological conditions such as multiple sclerosis ⁷ and Alzheimer’s disease. ⁸ 

Zonulin and blood-brain barrier permeability are dissociated in humans [2022]

There is a massive number of studies, speculations, and theories on addressing this issue, especially theories on fixing leaky gut. One example:

• Weight loss via a low-carbohydrate diet improved the intestinal permeability marker, zonulin, in prostate cancer patients. [2022]
• “Besides conventional treatments, several nutritional compounds including Colostrum bovinum (8), Apple-Derived Pectin (9), vitamins A and D (10) have been found to modulate the epithelial barrier by reducing serum levels of zonulin.” The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis [2020]

BBBP – blood–brain barrier permeability

First, we need to be aware that they are different: Zonulin and blood-brain barrier permeability are dissociated in humans [2022]. For a general discussion, see A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity [2020]

Some studies that are of special interest:

• Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine [2022] IMHO, for ME/CFS this is likely a very good combination.
• The molecular weight impacts the ability to cross the barrier ” An increase of the surface area of a drug from 52 A² (e.g., a drug with a MW of 200 Da) to 105 A² (e.g., a drug with a MW of 450 Da) dramatically decrease its BBB permeation [Blood-brain barrier permeation: molecular parameters governing passive diffusion].”

When dealing with neurological issues when there is a choice of several different substances, I have looked up the molecular weight and advocated for the lower molecular weight choice. For illustration,

• Acetylcysteine (N-acetylcysteine) has a weight of 163.19
• Minocycline has a weight of 457.5
• Azithromycin has a weight of 785
• Amoxicillin has a weight of 365.4
• Piracetam has a weight of 142 (this is a fast acting nootropic that clears brain fog in minutes for some people).
• Resveratrol 228, Quercetin 302, Curcumin 368, Aspirin 180

It is an easy way to do quick evaluation— for example, I would expect Resveratrol to have a greater effect on brain function than Curcumin, with Aspirin having a still greater potential effect.

Bottom Line

The purpose of this post is frame questions that may be relevant to you — and not provide general answers.

A reader reminded me of A short ME/CFS/MCS remission with microbiome samples [2019], which used uBiome. The toolset has changed a lot since those days, so I thought it would be a good learning activity to look at the samples with the new tools.

The person had a short remission from ME/CFS after:

• 19th-22nd Amoxicillin And Clavulanate
• 22-24th VSL#3

Analysis

The table below shows about the same number of bacteria identified but with an increase in the number of bacteria at extreme values. Condition Est. had a dramatic drop which would agree with the remission. We also see a dramatic drop in extreme Enzymes and Compounds.

In my humble opinion, it suggests that reducing extremes of enzymes and compounds is a desired objective goal.

Criteria	Current Sample	Old Sample
Lab Read Quality	9.1	8.1
Bacteria Reported By Lab	327	303
Bacteria Over 99%ile	8	5
Bacteria Over 95%ile	38	22
Bacteria Over 90%ile	70	56
Bacteria Under 10%ile	38	21
Bacteria Under 5%ile	24	11
Bacteria Under 1%ile	8	5
Lab: uBiome
Rarely Seen 1%	3	1
Rarely Seen 5%	26	4
Pathogens	26	24
Outside Range from JasonH	7	7
Outside Range from Medivere	16	16
Outside Range from Metagenomics	8	8
Outside Range from MyBioma	11	11
Outside Range from Nirvana/CosmosId	16	16
Outside Range from XenoGene	31	31
Outside Lab Range (+/- 1.96SD)	16	17
Outside Box-Plot-Whiskers	122	78
Outside Kaltoft-Moldrup	156	102
Condition Est. Over 99%ile	0	0
Condition Est. Over 95%ile	0	1
Condition Est. Over 90%ile	1	11
Enzymes Over 99%ile	0	0
Enzymes Over 95%ile	50	32
Enzymes Over 90%ile	148	94
Enzymes Under 10%ile	80	246
Enzymes Under 5%ile	45	50
Enzymes Under 1%ile	6	1
Compounds Over 99%ile	3	182
Compounds Over 95%ile	16	465
Compounds Over 90%ile	27	535
Compounds Under 10%ile	81	319
Compounds Under 5%ile	76	237
Compounds Under 1%ile	72	70

Spot Checking Specific Bacteria Shifts

The more extreme bacteria shifts are shown below. The drop of Faecalibacterium levels was likely due to the drop of lactic acid produced by Lactobacillus [Metabolic Response of Faecalibacterium prausnitzii to Cell-Free Supernatants from Lactic Acid Bacteria 2020]. Given that the person has a ME/CFS diagnosis, my thoughts point to the massive reduction of Lactobacillus caused by Amoxicillin and Clavulanate resulting in a drop of lactic acid (see Lactic Acidosis in ME/CFS). While the bacteria producing lactic acid may be killed, it takes time for the system to clear it. Some sources cite a half life of 18 hours in the body[src]. The VSL#3 may be incidental or may have contributed to the remission ending.

Bacteria	Newest Percentile(Percentage)	Older Percentile(Percentage)
(genus) Alistipes	31 (0.9%)	89 (5.7%)
(genus) Anaerococcus	97 (1.8%)	62 (0.08%)
(genus) Bifidobacterium	87 (3.6%)	96 (7.3%)
(genus) Erysipelatoclostridium	99 (3.9%)	69 (0.7%)
(genus) Faecalibacterium	19 (3.9%)	51 (12.1%)
(genus) Finegoldia	99 (3.5%)	68 (0.1%)
(genus) Intestinibacter	79 (0.4%)	97 (2.4%)
(genus) Klebsiella	91 (1.3%)	none
(genus) Kluyvera	89% (1.8%)	none
(genus) Lactobacillus	67 (0.01%)	97 (3.5%)
(genus) Megasphaera	96 (2.6%)	76 (0.01%)
(genus) Parabacteroides	95 (7.0%)	81 (3.5%)
(genus) Streptococcus	99 (7.3%)	13 (0.003%)

Bottom Line

Short term remission causes are often difficult to identify the cause. In this patient, the evidence appears to be for a model of Amoxicillin and Clavulanate being effective against existing lactic acid producing species (i.e. Lactobacillus). It takes time for the lactic acid to clear the body. On the flip side, the lactobacillus would start regrowing and producing lactic acid (thus ending the remission).

A compounding factor is “Antibiotic Resistance of LACTOBACILLUS Strains [2019]”

For the subset of people with ME/CFS that improves on antibiotics and then regress; it is likely because the antibiotic suppress (but does not eliminate) lactic acid bacteria which then regrows…

Question:

Quick question—I noticed, for my BiomeSight-via-Ombre sample, that I’m not getting Vitamins, Minerals and similar suggestions. I used to get them on this sample. This only happens when I set the “Everything” option.

Anything I might be doing wrong? I’m generating the suggestions with the KM, Box Plot whisper, and Standard Lab Ranges. Avoiding Special Studies per your recent advice.

Answer: No Reproduction

I did a video to show what I did and the results.

Hi I’m a 15 year CFS sufferer with severe GI / neuro problems.  I got my second Thryve results recently.  They look really quite normal to me and it says I have significant diversity.  Is there any help / analysis you could provide to help me narrow down if there’s something actionable?  I’m not sure how much capacity you have for that, but it doesn’t hurt to ask.

  And unfortunately have been sick for longer.  Got sick at age 25 with an infection (low grade fever for months), lost 30 pounds, had vision problems, headaches, fatigue and so on.  I was able to work four years in this state but eventually I had much worsening neuro and vision symptoms and was unable to work.  I developed POTS a couple years later and at times was using a walker to get to the bathroom and was bedbound.  I’ve had some episodes of vision loss that are very strokelike in that they debilitated me cognitively and visually for long afterwards (the vision loss itself resolves after some minutes or hours).

I want to emphasize the visual and cognitive impairment are totally debilitating.  I can barely read anything or reliably focus my eyes on anything, and I went from a previously extremely high functioning person to feeling drugged, barely here 24/7.  I have severe eye pain all the time.

So I’ve been sick for really my whole adult life, to varying degrees.  Primary debilitation is visual and cognitive but I have severe physical fatigue, POTS, am 30 pounds underweight, have been diagnosed with gastroparesis years back I just can’t keep the pounds on.  Also it is notable food makes me feel TERRIBLE. Right away I can feel stupid and drugged from it, but also 2-5 hours later is when I ache everywhere and get tired and non-functional.  The 2-5 hours I’m presuming is from some dysbiosis but right away is a little more puzzling.

I clearly have such bad digestion that it is not hard to imagine it is perpetuating my brain / eye / POTS symptoms.  I’ve tried everything under the sun, mainstream and holistic and nothing that is supposed to help the gut helps.  I think fasting gives me some relief but is not practical for someone so underweight.

My first thryve was on January 13, 2020.

My most recent thryve (now ombre) was October 2, 2022.

In between the two times I’ve cycled through several gut protocols, such as taking s boulardii, soil probiotics, bifidobacteria, sourkraut, and polyphenols.  Other times I tried a more killing oriented protocol with oregano oil, berberine, and once based on a stool test a prescription antifungal (sporonox).  I eat a very restricted diet and seem to react to pretty much every food, but I have cycled through different foods in the last couple years.  I’ve tried prebiotics like PHGG and lactulose recently and are finding at least in the short term I am losing weight and have worse neuro symptoms.

My digestion and overall symptoms have not really changed between the two times.  ombre says I have a quite high microbial diversity score which is surprising because I have a massive history of antibiotics.

The request

First Look at the sample

Comparing the samples, I see a much lower quality report (2.5) in 2020. It was interesting to see

• Bacteria Over numbers drop despite more bacteria is latest sample
• Bacteria Under numbers grew — which may be due to a better quality of sample (more bacteria)
• Two of my usual measures showed improvement (despite more bacteria) — Outside Lab Range, Outside Box-Plot-Whiskers while the last one showed an increase which was a smaller percentage than the increase of bacteria reported.
  • My impression is that objectively he appears better than in 2020.

Criteria	Jan-20	Sep-22
Lab Read Quality	2.5	8.5
Bacteria Reported By Lab	442	656
Bacteria Over 99%ile	10	2
Bacteria Over 95%ile	45	10
Bacteria Over 90%ile	88	23
Bacteria Under 10%ile	54	154
Bacteria Under 5%ile	21	94
Bacteria Under 1%ile	6	19
Lab: Thryve
Rarely Seen 1%	5	7
Rarely Seen 5%	28	37
Pathogens	32	32
Outside Range from JasonH	6	6
Outside Range from Medivere	16	16
Outside Range from Metagenomics	10	10
Outside Range from MyBioma	13	13
Outside Range from Nirvana/CosmosId	18	18
Outside Range from XenoGene	9	9
Outside Lab Range (+/- 1.96SD)	27	5
Outside Box-Plot-Whiskers	124	51
Outside Kaltoft-Moldrup	183	239
Condition Est. Over 99%ile	0	0
Condition Est. Over 95%ile	1	0
Condition Est. Over 90%ile	4	0
Enzymes Over 99%ile	12	190
Enzymes Over 95%ile	208	516
Enzymes Over 90%ile	457	585
Enzymes Under 10%ile	59	265
Enzymes Under 5%ile	20	154
Enzymes Under 1%ile	2	20
Compounds Over 99%ile	73	24
Compounds Over 95%ile	264	101
Compounds Over 90%ile	368	172
Compounds Under 10%ile	297	265
Compounds Under 5%ile	225	223
Compounds Under 1%ile	62	165

In terms of bacteria distribution (not “diversity”). we see an abundance of domineering bacteria (90-99) in the earlier sample which flipped to proliferation of weak bacteria (0-9). Have tons of small amounts of bacteria at low levels should result in a good diversity. The over-representation of these nominal bacteria is a concern to me.

His attempts to change was successful. Ideally we can help more change in the desired direction.

Approach

Using PubMed data, nothing stands out and we have a very short list. This simply means that there is not a good match to the conditions reported there. In terms of Dr. Jason Hawrelak Recommendations we are at 89%ile, so generally good. The main items missing the goals by his criteria are: Faecalibacterium prausnitzii, Lactobacillus, Bifidobacerium and Akkermansia.

Given no strong pattern to match against, I will build a consensus from Lab Range, Box-Plot-Whiskers, Kaltoft-Moldrup and Dr. Jason Hawrelak Recommendations

Cross validation to the literature on the above (i.e. seeing if any has been documented to help ME/CFS). Since neurological issues were called out (and I had just done another sample with this recommendation, a few more for Hesperidin)

• Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (NAC ME/CFS)
• Hesperidin
  • 8-Week Supplementation of 2S-Hesperidin Modulates Antioxidant and Inflammatory Status after Exercise until Exhaustion in Amateur Cyclists [2021]
  • Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence [2019]
  • The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway [2020]
• Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. [2015]
• “Promising results are obtained by treatment with Momordica charantia extract, ” News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments [2019]
• Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders [2019]
• Randomised clinical trial: high-dose oral thiamine[b1] versus placebo for chronic fatigue in patients with quiescent inflammatory bowel disease. [2021]
• The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient [1996]
• Response to vitamin B12 and folic acid[B9] in myalgic encephalomyelitis and fibromyalgia [2015]

So all of the top suggestions appear to have documented benefits for various subsets of ME/CFS. I use the term subsets because, while similar in some symptoms, there may be a lot of differences.

We also have the simplified suggestions (with dosages). This list is intended for the brain fog person.

Looking at this list, we see that he should consider using some of the probiotics he cited in his history: bacillus subtilis, bacillus clausii, bifidobacterium (animalis)lactis, bifidobacterium breve bifidobacterium infantis. We also have 3 lactobacillus which seems to often appear with ME/CFS samples: lactobacillus casei, lactobacillus gasseri and lactobacillus salivarius.

In terms of prebiotics, only chitosan was a positive. Selenium shows up as a strong recommended supplement. See the above download for more details.

Very atypically, KEGG probiotics reports very low recommendation values with E.Coli NOT being on the top of the list. I would keep to the above probiotics and ignore the KEGG list because of the low values.

Going over to the last, experimental, modelled food suggestions, Barley was the sole take. In terms of the consensus report, it’s a toss up with different variation being good to take or to avoid. Checking oats by itself, it’s a significant negative so I would exclude the last item below and suggests barley be considered.

Bottom Line

The top suggestions can all be verified in medical literature as helping ME/CFS and the suggestions are based on this individual’s microbiome — hence patient (and not study group) specific. Hopefully he will try them and in 3-4 months do another sample so we can evaluate the change (for better or worse — I want to learn, not be right).

Because of the weight issue, I would suggest trying Pendulum, the akkermansia probiotic. I noticed that it resulted in weight loss for me and recall that is also reported in the literature.

• Akkermansia muciniphila: A Next-Generation Beneficial Gut Microbe and Its Role in Obesity and Diabetes [2022]
• Akkermansia muciniphila Suppresses High-Fat Diet-Induced Obesity and Related Metabolic Disorders in Beagles [2022]
• Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes [2022]

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that appears to have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

I use modelling and various mathematical technique to estimate forecasts when there is no hard data available.