jinder

Not just that. In mice, SSRIs stop having any anti-depressant effects if the vagus nerve is severed: https://www.nature.com/articles/s41598-019-50807-8

So they also seem to be effective via the enteric nervous system!

While the serotonin used in your gut doesn’t directly impact the brain, it does impact the enteric nervous system which communicates via the vagus nerve to your brain. So I don’t think it’s correct to say this doesn’t (or couldn’t) impact your mood (and indeed murine experiments demonstrate it does).

Or perhaps there are significant links demonstrated in murine models of the multi-directional relationship of the gut-brain-immune axis, and that traditional models of disease are not sufficient to elucidate this?

Where is the best-in-class evidence that CBT is effective at treating long covid and chronic fatigue syndrome?

Some people really do have mast cell issues, but everyone and their dog thinks they have MCAS these days and it's questionable in my opinion. Often a diagnosis will be based on whether any of the MCAS-drugs work (rather than testing which is very problematic for MCAS). But as you see in the linked paper famotidine was effective in mice genetically engineered without mast cells, so at least in that instance it's not a mast cell issue.

The tricky thing with increasing butyrate production is that everyone's gut dysbiosis is different - and therefore, a prebiotic that works for one person may make someone else's condition worse. For example, I have big blooms in my Prevotella Copri population which would consume Inulin and make my butyrate production worse - but in people without a Prevotella Copri overgrowth, Inulin would improve their butyrate production.

I would look into 16S microbiome testing (I use Biomesight) and use that as a guide, as well as slowly trialing interventions and monitoring symptoms. None of this is perfect and you kinda have to be on the bleeding edge of science/alternative medicine to figure things out.

Famotidine an old school H2 antihistamine used for acid reflux (pre PPIs), was found to have an additional mechanism of action via activation of the vagus nerve to inhibit pro-inflammatory cytokines in covid (via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction - https://molmed.biomedcentral.com/articles/10.1186/s10020-022...).

It has also been used quite extensively to combat post-covid neuropsychiatric symptoms.

I think the link here is that increased LPS/endotoxin production by your microbiota can induce acid reflux, cause neuroinflammation and psychiatric symptoms. Low acid production itself can result in a more inflammatory microbiome further exacerbating the problem. Long term fix would be working on the migrating motor complex, improve motility/gastric emptying and rebalance the microbiome by reducing gram-negative bacteria/pathobionts and increasing butyrate production via selective feeding. [I'm not a doctor, this is just the direction I've been working on things myself]

What bust are you referring to? As far as I can tell there's still considerable development going on all around London.

How do Christian contemplative traditions predate Buddhism if Buddhism arose in the 5th century BCE?

How have you determined that the excess deaths are due to "covid restrictions" and not for example, long term sequelae of covid itself or other factors?

I think the independent status of the City of London is grossly exaggerated and not really comparable with the Channel Islands.

And what makes you think that?

Er no - the loss of a mother is extremely traumatic to a child. It can lead to long term mental health issues and physical health issues.

To get to the point of re-joining will take a long time with plenty of time for governments and minds in Europe to change.

Ultimately the EU is stronger with the UK as a member, and I’m sure if it’s willing to pay a high enough price it will be let back in (metrication, no-rebate, the euro etc).

I've used SSP and let's just say I think it's nothing short of revolutionary. It seems to be completely changing how my brain works and how quickly it gets activated (in the sense of what state it is in).

Try to be born vaginally rather than c-section (might be too late for that!), avoid antibiotics unless you absolutely need them, polyphenol-rich whole food diet with diverse fruits and vegetables, lots of fibre and resistant starch and fermented foods. Buy organic if possible.

My guess: Environmental toxins, antibiotic use and poor diet leading to loss of microbiome diversity/dysbiosis and consequential disruption to the body’s homeostatic processes.

GB is not more neutral - it excludes Northern Ireland, which is a part of the UK.

Yes - totally the opposite. In fact, I think the issue with Angular is that they've not finished the work to make Angular RX-everywhere (for example, reactive components need to be manually plugged into Subjects at the moment).

With RxJS you should use it everywhere (observing state, observing component inputs, side effects etc). It's when you use it half-heartedly that you get problems with merging different programming paradigms.

The biggest issue with RxJS that we've found is that some devs have a super hard time getting to grips with the paradigm, and if your project is mostly those types of people, it will end up a disaster.

You're correct - it appears to work via the gut-brain axis, see my comment above.

To add to my comment, this explains why SSRIs take some time to work - it's the signalling through the vagus nerve that takes time to impact the brain. Other compounds such as curcumin and famotidine (H2 antihsitamine) have also been found to work via this mechanism. For many many years scientists had dismissed curcumin as having no effect because it's not bioavailable - recent research has shown that it doesn't need to be if it directly activates your nervous system! There's a lot more research that needs to be done here, and I think promising therapeutics for impacting brain function are coming our way as researchers learn more.

If you consider the brain a state machine, inputs from the nerves - through gut-brain axis, through your eyes and ears (socialising, environmental cues, sounds of safety vs sounds of threat), through your skin (touch) etc all impact the state. This state can range from safety to fight-or-flight (anxiety) to shutdown (depression). This is hugely simplified (for example neuroinflammation, endotoxins/LPS etc can impact this also) but I've found it very useful for regulating my own state and understanding why I feel happy, agitated, low etc.

SSRIs appear to work through the vagus nerve in a similar way to psychobiotics. Their direct effects on neurotransmitters are probably an unwanted side-effect:

Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling (2019): https://www.nature.com/articles/s41598-019-50807-8

Identification of SSRI-evoked antidepressant sensory signals by decoding vagus nerve activity (2021): https://www.nature.com/articles/s41598-021-00615-w

No I don’t think it’s permanent - mine seems to be slowly and progressively improving. You almost have to retrain your autonomic nervous system on a step by step basis.

It's super super common for people to recover from covid, be okay for a few weeks or even months and then lapse into long covid. In fact, it's relapse-remitting for many people. If you have symptoms of dysautonomia, this can be barely symptomatic until you do something that triggers an exaggerated sympathetic nervous system response.

The vast majority of apps you see on the App Store, including most games can be web apps. So I'm not sure what your point is?

Apple has deliberately under-invested in implementing web platform features on Safari. If you've tried to build a web app on Safari vs Android Chrome, you'll know what I mean. It's not a conspiracy - it's a clear as day policy to keep consumers and developers locked into their platform.

Correct - after years of deliberately hobbling Safari so you couldn't build quality app experiences, they suddenly start releasing lots of useful improvement just as regulators are sniffing around.

PHGG, GOS and lactulose (if you don't have SIBO) are relatively good prebiotics in my experience. However, the type of prebiotics you use should be tied to what's going on in your microbiome. Some common ones, such as Inulin, can feed both good and bad bacteria (and good bacteria become bad if they overgrow).

Biomesight is the best 16S provider right now in my opinion. They use Jason Hawrleak reference ranges and interventions as far as I’m aware. However this sort of testing only gives you an overall picture, is pretty variable and works in percentages.

I’ve been shifting my microbiome for the best part of a year, and boy is it difficult, especially if you have non-trivial issues. I think there’s a huge space here for potential startups that can start capturing research into actionable intervention steps (nobody is doing it well at the moment).

I'm sure you could - but if you went about it scientifically there would easily be thousands (not just the 3 in Ayurveda). That being said, I do think Ayurveda is mostly about manipulating the microbiome, and I think there are probably real nuggets of truth in its approaches. For example the use of Triphala to improve motility will help in numerous dysbiotic states.

I think the reality is closer to different dysbiotic states can cause depression. Depending on the the specific dysbiosis, the interventions will be different.

Many antidepressants are (e.g. Mirtazapine), but not Sertraline (Zoloft).