Gut dysbiosis is a hidden cause of Long COVID and you might not even have the symptoms

Long COVID is when, after someone “recovered” after getting COVID, they still retain a lot of symptoms, such as (R):

  • Fatigue
  • Anxiety
  • Muscle weakness
  • Poor endurance
  • Sleep difficulties
  • Depression
  • Prolonged malaise
  • Loss of smell
  • Poor cognition
  • Paintful joints
  • Sleep difficulties
  • Diarrhea
  • Poor glycemic control
  • etc.

The main symptoms are fatigue and/or muscle weakness (63%), sleep disturbance (26%), dyspnea (23%), anxiety/depression (23%), hair loss (22%), loss of test/smell (7–11%), chest pain (5%), and diarrhea (5%) (R).

And it’s not just a small amount, but a surprisingly large amount. A meta-analysis including 47,910 patients found that about 80%, developed at least one chronic symptom, particularly fatigue and dyspnea (R).

There are many theories as to why people get long COVID, some of which include persistent dysregulation of the immune system, hypometabolism, etc.

I want to talk about another reason. One of the theories that play a much bigger role than what people think, is the gut angle.

ACE2 & COVID

By now we all know that both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs.

ACE2 is part of the renin-aldosterone-angiotensin-system (RAAS).

ACE1 converts angiotensin I to angiotensin II, which has inflammatory, fibrotic and vasoconstrictive properties. Angiotensin II binds to the angiotensin type I (AT1) receptor.

ACE2 converts angiotensin II to angiotensin 1-7, which has anti-inflammatory and vasodilation properties.

The virus, when it binds to ACE2, reduces its expression, which leads to high angiotensin II and low angiotensin 1-7.

Different reports state that ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs), both inducing the expression of ACE2, may be beneficial in COVID-19 (R). Because it shifts the balance towards a better Angiotensin 1-7 to Angiotensin II ratio.

Another mechanism of action of ACE2 is to control amino acids absorption, specifically tryptophan.

Dietary tryptophan is primarily absorbed via the B0AT1/ACE2 transport pathway in the small intestinal epithelial cells, and this results in the activation of the mammalian target of the rapamycin (mTOR) pathway, which regulates the expression of antimicrobial peptides. These antimicrobial peptides can affect the intestinal composition of the gut microbiota [160,161]. As previously mentioned, the SARS-CoV-2 S protein binds ACE2 and, when SARS-CoV-2 blocks ACE2, it also blocks B0AT1, and thus tryptophan cannot get absorbed efficiently, which leads to the aberrant secretion of antimicrobial peptides and consequently to an altered microbiota [162]. Noteworthy, these changes also confer susceptibility to inflammation of the large intestine [160,162].” (R)

So too little ACE2 can lead to reduced tryptophan uptake, which leads to insufficient antimicrobial peptide release and dysbiosis. This unabsorbed tryptophan can then be used by bacteria to create metabolites that aren’t beneficial for the human body.

Long COVID and gut dysbiosis

A lot of us know that ACE2 is expressed in the respiratory system, that’s why people got a cytokine storm there and get respiratory disease.

But the lungs don’t even have the highest ACE2 expression in the body.

ACE2 expression levels were the highest in the small intestine, colon, testis, kidneys, heart, thyroid, and adipose tissue, medium expressed levels in the lungs, colon, liver, bladder, and adrenal gland (R, R, R).

So the gut is actually hit harder than the respiratory tract.

Amount of fecal calprotectin, a marker of intestinal inflammation as a consequence of translocation of granulocytes and monocytes/macrophages into the gut lumen, was elevated in feces of patients with COVID-19 [39], indicating immune dysfunction of the gut and altered gut niche in COVID-19 patients.” (R)

Inflammation in the small and large intestine (due to the virus binding to ACE2 and causing a cytokine storm) can lead to:

  • Damage to the villi, which will lead to reduced nutrient absorption
  • Reduced and increased transit time (initial short transit can over time lead to long transit time due to cellular energy deficiency. Slow transit time doesn’t necessarily mean constipation)
  • Reduced gut bacterial diversity (R)
  • Reduced release of anti-microbial peptides, which can lead to SIBO, dysbiosis, IBS, etc.
  • Reduced NAD and enterocyte energy levels
  • Accumulation of serotonin, which contributes to IBS and IBD
  • Leaky gut, microbial translocation and enhanced absorption of lipopolysaccarides (endotoxin) and other bacterial toxins (R).

And the consequences of the above range from Parkinson’s, to kidney, liver and heart failure to Long COVID.

Dysbiosis, which is defined by alternations in gut bacteria, mainly by an increase in more pathological bacteria and a decrease in benign bacteria. This causes more inflammation and problems in the long run.

Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the re-assembly of the gut microbiome post COVID-19.” (R)

In essence, the viral infection causes dysbiosis (or worsens dysbiosis) which exacerbates symptoms. After most of the COVID symptoms have passed, dysbiosis remains, which contributes to long COVID symptoms.

Concordantly, long-lasting gut microbiome dysbiosis is also consistently observed in subjects recovered from COVID-19 [12, 15, 27, 28], implying that gut microbiome is closely linked to host health in a post-COVID-19 age.” (R)

The inability to revert back to a normal microbiome is what significantly worsens everything.

Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread.” (R)

Lastest reviews

Love it!

Rated 5 out of 5
September 12, 2021

Love the newsletter and all the community work you do. Just gave the newsletter 5 🤩 !

Christian

Why the gut plays such a big role in Long COVID

Now that we know that gut inflammation and dysbiosis are common amongst those with long COVID, let’s look at why it can be causative, and not only an association.

Upcoming articles:

  • Gut-immune axis and long COVID (70-80% of the immune system is in the gut)
  • Serotonin and long COVID (excess serotonin has been found in the gut of people suffering from COVID)
  • Glutamate to GABA ratio and long COVID
  • Endotoxin and long COVID

Stack

Gut dysbiosis is present in a lot of people with Long COVID even if they don’t have obvious gut disturbance symptoms.

The gut can influence how you feel in many different ways, through for example the gut-brain axis, gut-lung axis, gut-muscle axis, etc. More and more “axises” are being discovered, but I think it’s safe to say there is a gut-everything else axis.

In order to resolve Long COVID symptoms, it’s important to fix underlying gut problems.

So stopping viral replication and also inflammation in the gut is fundamental for recovery.

And I know just the perfect supplements for that.

Lapodin

Lapodin contains the quinones emodin and beta-lapachone. If you recall, I talked about how beneficial quinones, like emodin, are for the gut in last week’s newsletter (#4)

Emodin not only “fixes” dysbiosis and prevents leaky gut, but it also inhibits the binding of SARS-CoV spike protein and ACE2.

Ho et al.18 showed that, 1,3,8-trihydroxy-6-methylanthraquinone (emodin) can block interaction between SARS-CoV spike protein and ACE2, with 94.12% inhibition at 0.05 mM.” (R)

Nigella sativa

Next up is Nigella sativa or black cuminThymoquinone, the main constituent of Nigella sativa, has strong anti‐inflammatory and antimicrobial activities and has recently been shown to possibly inhibit SARS‐CoV‐2 and interfere with its binding to ACE2 receptors (R).

It’s also been shown to protect the intestinal mucosa, suppress the growth of potentially harmful gut microbiota, prevent endotoxin-induced depression-like behavior (in animals) and even decrease the levels of early‐stage sepsis biomarkers (e.g., ESM‐1, CRP, and VEGF) by ~30–50% (RR).

LL-37

Lastly, we have LL-37. LL-37 is an antimicrobial peptide (AMP) found in the gut. Vitamin D stimulates the transcription of cathelicidin which is cleaved to generate LL37 and we know by now how great vitamin D is against COVID. Certain bacteria can upregulate LL-37 to kill off their competitors. LL-37 is also naturally upregulated by butyrate and we know that butyrate-producing bacteria are significantly lowered in those with COVID-induced dysbiosis.

And finally:

SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2.” (R)

Stack

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.