December 19th, 2022

The new world of Omicron is a constant deck chair shuffle regarding which strain holds court and for how long. It appears that a few months is the max a strain maintains the chairs. China is heading into a massive illness burden which could alter the frequency of the mutations.

None of these VOC's are showing signs of increased disease morbidity.

Little else to report here. (CDC Variants)

 Quick Hits and other musings -

1) More on vaccines in young adults men from JAMA: "Question What are the frequency, clinical features, and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in adolescents and young adults? Findings: In this systematic review and meta-analysis of 23 studies, including 854 patients aged 12 to 20 years with vaccine-associated myopericarditis, the incidence of myopericarditis was higher in males after the second dose.

Although 15.6% of patients had left ventricular (LV) systolic dysfunction, only 1.3% had severe LV systolic dysfunction (ejection fraction <35%); late gadolinium enhancement was found in 87.2% and 23.2% required intensive care unit admission; however, no in-hospital mortality was observed. Meaning: These findings suggest largely favorable outcomes of COVID-19 vaccine-associated myopericarditis in adolescents and young adults." (Yasuhara et. al. 2022) This data, yet again, reinforces within me the lack of need to vaccinate this group moving forward.

2) In a large cohort study by Kwan and colleagues we see a strong association between Positional Orthostatic Tachycardia Syndrome, POTS, and SARS2 infection or vaccination. Infection remains more risky than vaccination, however, it is clear that the mRNA vaccines against SARS2 did and still will trigger the disorder POTS. (Kwan et. al. 2022) This data puts more emphasis on the need to understand why some people suffer chronic fatigue/POTS post viral illness and to try and change the downstream risk as these viral illnesses are here to stay. As with Guillan Barre and other post viral disorders, vaccines can induce the same issue.

3) "Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue–resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue–resident macrophages." (Martinez-Colon et. al. 2022) Obesity is associated with all cause mortality in humans. Covid is a new addition to the reasons why being overweight is a net massive negative to health over a continuum.

4) The year without germs is an article in the Atlantic that is interesting. (Wu. K 2022) Give it a read.

 

Neurological diseases like Parkinsons and Depression are in the news again with links to abnormal bacterial microbiomes.

First from Nature Communications: "Parkinson’s disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end... Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were observed in experimental models." (Wallen et. al. 2022)

The authors found that the oral bacteria Bifidobacterium dentium, Actinomyces oris and Streptococcus mutans were over represented by 6-7X. Roseburia intestinalis and Blautia wexlerae were under represented by 5-7X. The data describes a picture whereby these 30+% of Parkinsons associated bacterial species were significantly altered in abundance leading to a 1-7X increase or decrease in PD when compared to a control population.

"Alpha-synuclein pathology has been detected in the gut of persons with PD at early stages, and there is evidence from imaging studies that in some cases pathology may start in the gut and spread to the brain. In mice, it was shown that alpha-synuclein fibrils injected into gut induce alpha-synuclein pathology which spreads from gut to brain, and that vagotomy stops the spread. In parallel, large epidemiological studies have shown that persons who had complete truncal vagotomy decades earlier had substantially reduced incidence of PD later in life." (Wallen)

This bit of evidence is remarkable as we see direct evidence that the vagus nerve mediates this activity from the gut to the brain. The gut is the ground zero as far as the current data is teaching us.

This begins another layer of why these diseases have been so hard to understand and treat because we have potentially been looking into the late downstream affected area instead of the upstream source of the disturbance.

Let us look at a second paper in Nature Communications. This time the authors are looking at depression and the microbiome of the intestine. "We identify association of thirteen microbial taxa, including genera Eggerthella, Subdoligranulum, Coprococcus, Sellimonas, Lachnoclostridium, Hungatella, Ruminococcaceae (UCG002, UCG003 and UCG005), LachnospiraceaeUCG001, Eubacterium ventriosum and Ruminococcusgauvreauiigroup, and family Ruminococcaceae with depressive symptoms. These bacteria are known to be involved in the synthesis of glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters for depression. Our study suggests that the gut microbiome composition may play a key role in depression." (Radjabzadeh et. al. 2022)

It has long been thought that the gut, brain and immune connection is the key to neurological disease in modern society. Now we are getting study after study demonstrating concrete linkage and pathophysiological mechanisms leading to this cause and affect reality.

As discussed time and again within these pages, we must take care of our intestinal friends through proper lifestyle choices including movement, nutrition, stress reduction and toxin avoidance.

The vagal nerve influence is especially interesting as trans vagal nerve stimulators (tVNS) could have an effect long term on reducing vagal dysfunction that could be a part of this issue as well. I posed this question to a friend and here are his thoughts paraphrased:

What would be the difference between a vagus nerve that is active and working towards your relaxed health and one that is not working? The vagus nerve carries a current bidirectionally and there is an electromagnetic field that follows the current as it travels. The vagus nerve, when firing, is an aggregation of nerve impulses and their associated EM effects. This nerve always has some current flow. It's a question of how much.

In the research the vagus nerve when cut had major effects.
3 possibilities
• The vagus nerve is intact and not firing much. It could be used by bacteria to climb up into the brain.
• The vagus nerve is intact, firing often and associated with a strong electromagnetic field. Hypothetcially, this could interfere with cellular processes of bacteria killing those that try to climb up from gut to brain. (Bennaroch et. al. 2020)
• The vagus nerve is not intact and can't be used by bacteria to climb into the brain.

The middle choice seems to be the best version for a hypothetical solution to this issue. See below for the science from the article.

It may be a treatment of the future to use tVNS to treat neurological diseases related to dysbiosis. Stay tuned!

That's all this week,

Dr. M

Yasuhara JAMANetwork
Kwan Nature Cardiovascular Research
Martinez-Colon Science Translational Medicine
Wu Atlantic
Wallen Nature Communications
Radjabzadeh Nature
Benarroch Trends in Microbiology
CDC MMWR
CDC Variants Page
CDC Covid Deaths

"For several decades, electrophysiology was remote from the concerns of most microbiologists. The recent realization of signaling roles of bacterial membrane potential dynamics has begun to draw the attention of researchers to the roles of membrane potential dynamics in the microbiological phenomena of interest, many of which remain unexplored. For example, it is now conceivable that electrical signaling may mediate host–microbiota interactions. We also foresee a future where bacterial cellular behaviors and functions can be controlled using electricity – in a similar manner by which neurons and muscles are controlled. Such technologies may offer an electrical approach to treat antimicrobially resistant pathogens. It could also allow precise spatiotemporal control of industrial bioreactors for improved productivity. Development of electrical interfaces to bacteria and electrobacterial hybrid systems would facilitate the convergence of bioelectronics and synthetic biology. Yet, electrophysiology is still a largely uncharted territory in microbiology. For this reason, we argue that bacterial electrophysiology approaches hold unrealized promise of making exciting new scientific discoveries and societally valuable technology developments." (Benarroch et. al. 2020)