Gut microbiome alterations in children with AIS

[Dingo]

The Cotrel White book MRI studies in Hong Kong of the inner ear and cord malformations were pretty conclusive...I posted in the research section a few months ago. Left inner ear, right thoracic. Those studies make one wonder if we are all congenital scoliosis patients. There has to be a cause even if its before the curve. You can have a cause and a delay which presents another problem that needs to be figured out.

I must have missed that. Do you have a link to that study? That's interesting.

Because of the discovery of the Syrinx in Scott's MRI I think there is a good chance his case was congenital. This is especially true since his curve was discovered at age 4.

I don't think JIS or AIS applies to him. It was probably the cyst.

[titaniumed]

Here you go....

http://www.scoliosis.org/forum/showt...changes-in-CNS

Ed

[titaniumed]

The reason there are large kyphoses in the UK and why we have children with large scoliosis in Canada are directly attributable to the wait times. Elias in Canada had a huge curve and STILL was never scheduled. If Shriners in the US didn't take him who knows how big it would get. And Canada is a first world country. Multiply that problem for African counties where the wait time is approaching infinity if it isn't already infinite for most kids.

Idiopathic scoliosis is about 2-3% all over the world. Therefore the INCIDENCE of IS in the US and UK and Africa is probably similar with the possible exception of the UK and that area of the world where there seems to be an additional genetic predisposition over and above the 2-3% genetic predisposition.

Given similar incidence, the PREVALENCE of large curves is controlled by availability of treatment. Knowing the availability we can accurately predict that there will be more large curves in the UK than in the US and more large curves in African compared to both the US and UK. And that is what we see.

For non-idiopathic cases like those due to polio, the incidence and prevalence are controlled by the incidence of polio virus or other viruses or bacteria. For countries that don't have vaccination programs, the incidence and prevalence of scoliosis due to these causes and not idiopathic is whatever it is. It may or may not be higher than the 2-3% for IS all over the world. I hope it much lower. We have eradicated small pox worldwide so I think there must be worldwide vaccination programs for other diseases. If so, most of the scolioses in Africa are probably still idiopathic scoliosis, many/most of which go unfused and so become large.

Sharon, this was well written.

Here is a severe case from Dr Hey last week. 15 years old, with a 90.
https://drlloydhey.blogspot.com/2018...ee-had-40.html

Dingo caught Scott right at the right time. (for tethering)


Ed

[Pooka1]

Sharon, this was well written.

Here is a severe case from Dr Hey last week. 15 years old, with a 90.
https://drlloydhey.blogspot.com/2018...ee-had-40.html

Dingo caught Scott right at the right time. (for tethering)


Ed

Wow amazing case! I didn't realize Dr. Hey was still writing his blog. Thanks for ED-ifying me. :-)

[titaniumed]

When I had my tap for a CT looking for things, in 2002 (before Dr M) I asked that doctor if they pulled a sample of my spinal fluid for study. He replied why, and I gave up.

There is some reason why curves "accelerate" the way they do. We need to answer why some diseases are slow acting, and some are so aggressive.

Like approaching a highway with no speed limit, 20 degrees in a kid can be like a highway with no speed limit.

Ed

[Dingo]

Here you go....

http://www.scoliosis.org/forum/showt...changes-in-CNS

Ed

Now I remember!

[Dingo]

When I had my tap for a CT looking for things, in 2002 (before Dr M) I asked that doctor if they pulled a sample of my spinal fluid for study. He replied why, and I gave up.

There is some reason why curves "accelerate" the way they do. We need to answer why some diseases are slow acting, and some are so aggressive.

Like approaching a highway with no speed limit, 20 degrees in a kid can be like a highway with no speed limit.

Ed

If inflammation plays a role it starts to make sense.

1) More inflammation = more curve progression
2) More curve progression = more inflammation

So maybe it's just a feedback loop.

The fact that in the Zebrafish model Scoliosis could be treated with NAC (a simple NSAID) might tell us everything.

Scoliosis might be caused by harmful inflammatory processes... which would make it like practically every other disease.

Google just about any common disease and add the word inflammation. It's ubiquitous.

[titaniumed]

NSAID's are incredible meds for pain and inflammation. I started with Celebrex in 2002, Bextra, Naproxen, and Diclofenac. Back in 2002, they used to hand them out like candy. Of course, this has all changed. I don't think doctors prescribe these to kids. ?? Wouldn't it be something if they reduced curves?

It would be interesting if they could establish "exactly" what and which infection a human patient has. It seems that this only happens upon Staph and P-Acnes etc after its a problem. If its in the spinal fluid, they should take a look at this, after all, it only circulates up into the brain. Since the spinal cord plays a significant role in the CNS system, it would seem that this would be a huge FLAG stating, "Look at me". They could do this upon scoliosis surgery, or before with a spinal tap. There has to be some sort of reason why this isn't being done, the scoliosis surgeons and neurologists have to be thinking about this.

Unless its a human in a Zebrafish suit, its still a Zebrafish study.

The farm bill will be signed into law tomorrow. Hemp and CBD will become legal on a federal level. This relaxes things as far as medical research goes in the CBD arena....In the meanwhile, its going to explode and people will be taking a product that has no FDA approval. I can imagine there will be manufacturing on every street corner with substandard quality control. Mass marketed chemical exposure before the scientists determine anything. CV Sciences has a GRAS certificate. "Generally regarded as safe"

I have heard that it works well for anxiety.....

Ed

[Dingo]

It would be interesting if they could establish "exactly" what and which infection a human patient has. It seems that this only happens upon Staph and P-Acnes etc after its a problem. If its in the spinal fluid, they should take a look at this, after all, it only circulates up into the brain. Since the spinal cord plays a significant role in the CNS system, it would seem that this would be a huge FLAG stating, "Look at me". They could do this upon scoliosis surgery, or before with a spinal tap. There has to be some sort of reason why this isn't being done, the scoliosis surgeons and neurologists have to be thinking about this.

In AIS the inflammation might be in the spine but the root of the problem could in theory be somewhere else.

In the case of Rheumatoid Arthritis it appears that the problem is in the stomach even though the inflammation is in the joints.
The Gut Microbiome and Rheumatoid Arthritis: Understanding the Connection

The same appears to be true for Multiple Sclerosis. The problem appears to be in the stomach but the inflammation is in the nervous system.
Gut germs play role in multiple sclerosis, studies show. Are probiotics for MS next?

In theory it all makes sense.
1) Scott was born with a Syrinx which resulted in inflammation in the spine which lead to Scoliosis.
2) A child in Africa suffers from Tuberculosis which penetrates the spine, causes inflammation and leads to Scoliosis.
3) The Zebrafish have a gene that for reasons that aren't yet understood triggers inflammation in the spine which leads to Scoliosis.
4) Maybe in AIS something is wrong in the stomach, similar to MS or RA this triggers inflammation in the spine which once again leads to Scoliosis.

It could be that Scoliosis in young people is always triggered by inflammation in the spine but there might be a dozen different starting points.

If someday researchers prove that Scoliosis can be treated with something as low tech as Aspirin... holy cow. Somebody should have tested that a long time ago.

[Pooka1]

Here is a good paper showing how bad the literature is and how there is not much evidence to link other anomalies to AIS...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018432/

PLoS One. 2014; 9(5): e97461.
Published online 2014 May 12. doi: 10.1371/journal.pone.0097461
PMCID: PMC4018432
PMID: 24820478

How ‘Idiopathic’ Is Adolescent Idiopathic Scoliosis? A Systematic Review on Associated Abnormalities
Tom P. C. Schlösser, 1 Geert J. M. G. van der Heijden, 2 , 3 Anne L. Versteeg, 1 and René M. Castelein 1 , *
Bart O. Williams, Editor

Abstract
Background
Despite more than a century of dedicated research, the etiology and pathogenesis of adolescent idiopathic scoliosis (AIS) remain unclear. By definition, ‘idiopathic’ implies an unknown cause. Nevertheless, many abnormalities concomitant to AIS have been described, often with the suggestion that these abnormalities are related to etio-pathogenesis. Insight in the concomitant abnormalities may assist in improving the understanding of the etiological pathways of AIS. We aimed to systematically review and synthesize available studies on abnormalities concomitant to AIS.

Methods
Original studies comparing untreated AIS patients with healthy adolescents on abnormalities other than the deformity of the spine were retrieved from PubMed and Embase. We followed PRISMA guidelines and to quantify the relationship between each abnormality and AIS we used a best-evidence-syntheses for relating risk-of-bias to consistency of effect sizes.

Results
We identified 88 relevant citations, forty-seven carried high risk-of-bias and twenty studies did not report quantitative data in a sufficient manner. The remaining twenty-one publications failed to report data from before initiation of the deformity and blind assessments. These cross-sectional studies provided data on fourteen abnormalities concomitant to AIS. With our best-evidence-syntheses we were unable to find both strong evidence and a consistent pattern of occurrence for AIS and any of these abnormalities. From moderate risk-of-bias studies a relatively consistent pattern of occurrence for AIS and impaired gait control (4 studies; 155 subjects; Cohen’s d = 1.00) and decreased bone mineral density (2 studies; 954 subjects; Cohen’s d = −0.83) was found. For nine abnormalities a consistent pattern of occurrence with AIS was found, but the evidence for these was weak.

Conclusions
Based on the available literature, strong evidence is lacking for a consistent pattern of occurrence of AIS and any abnormality. The relevance for understanding the multifactorial etiology of AIS is very limited.

[Pooka1]

A gastroenterologist on DoctorRadio recently mentioned that not only is very little known about the gut microbiome but that it is so complex that we are years, decades away from showing any specific connections with disease or illness. So any studies out there claiming to show something are likely false for the reasons mentioned in the paper I posted.

[titaniumed]

Decades is such a depressing word in the scoliosis world, but still better than Centuries....

Our bodies are so complex....Sigh....

Ed

[Pooka1]

Decades is such a depressing word in the scoliosis world, but still better than Centuries....

Our bodies are so complex....Sigh....

Ed

We are still at the point where there is no strong evidence for probiotics which are bacteria. If we can't get anywhere with that then I am not sure how we are going to figure out the much more complex problem of bacterial association with disease.

The real challenge with the gut microbiome is not just trying to find true disease associations and not just statistical correlations like have been found to date but to clearly demonstrate cause and effect. Scoliosis and even idiopathic scoliosis are such mixed bags that it its going to be even harder to show true findings against that background. The gastro guy didn't make reference to scoliosis but was talking generally how new the gut microbiome field is and that there is almost nothing known that is real. Simple correlations are not likely going to be a true answer when we can't even identify the bulk of feedback loops that likely exist in such a complex microbial community as the gut.

[Dingo]

I'm not sure what that Dr. said on the radio station but scientists are lot further along than that.

This just in: Yale researchers ameliorate Lupus with resistant starch dietary intervention in TLR7-dependent Lupus mouse model.

News article: December 20, 2018 - Yale University - Impact of diet intervention on autoimmunity in mice
Full study: Cell Host & Microbe: A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

(I encourage anyone interested in the microbiome to read the full study, it's fascinating)

Because diet can shape gut microbial communities and also influence host immune processes (Kau et al., 2011), we used a dietary intervention to suppress lupus-related pathobionts. Fiber-rich diets such as RS are beneficial for pathogen resistance andmetabolic diseases that share inflammatory features with SLE (Desai et al., 2016; De Filippo et al., 2010; Ganguly, 2018; Sonnenburg and Sonnenburg, 2014). We were able to show that RS suppressed the abundance of L.reuteri in its ileal niche and prolonged survival of lupus-prone mice. Besides inhibiting the abundance of lupus-related pathobionts, RS also increased bacterial taxa capable of fermenting fiber into SCFAs; loss of their abundance having been linked to disease (De Filippo et al., 2010; Koh et al., 2016; Macia et al., 2015; Walker et al., 2011). Interestingly, bacteria from the order Clostridiales, which are known to promote mucus thickening (Wlodarska et al., 2015), were reduced in Lactobacillus-colonized SLE patients and lupus-prone mice. RS feeding of mice increased this order not only in fecal but also in cecal microbiomes. All three major SCFAs—acetate, butyrate, and propionate—were significantly elevated in the ileum of RS-fed mice, supporting local effects in the niche of L. reuteri.

In summary, the current study highlights the relevance of diet microbiota-host interactions in the development of autoimmunity and defines a link between pathobiont outgrowth and disease manifestations. Mechanistically, the pathobiont instigates the pDC-IFN axis in lupus-prone animals with excessive TLR7 signaling that results in impaired gut barrier integrity. The rapid rise of chronic immune diseases, which is paralleled by major changes in modern diets, might be related to mechanisms such as those we uncovered here. A lack of dietary fiber might allow for outgrowth of pathobionts that promote immune pathways in genetically prone individuals. These processes ultimately lead to the onset of systemic inflammatory conditions. Dietary or other targeted approaches toward the gut microbiota would restore homeostasis by restraining disease-promoting pathobionts (Lemon et al., 2012). Dietary interventions such as RS could bypass major side effects related to broad-spectrum antibiotics (e.g., antibiotic resistance or systemic toxicities). The appropriate diet would be expected to enrich beneficial commensals or metabolites that naturally control pathobiont overgrowth. In the future, asymptomatic but autoimmune-prone individuals with heightened pDC and type I IFN pathways might benefit from personalized diets tailored to their microbiota composition (Bourn and James, 2015; Kau et al., 2011). Because the type I IFN pathway is involved in various chronic inflammatory and metabolic diseases, identifying strains in the microbiota that fuel this pathway might have implications beyond autoimmunity (Ganguly, 2018).

However if you aren't fond of "science-speak" or not interested in reading the full study let me break it down to something that is actionable and easy to understand.

1) Eat fruits, vegetables and other non-processed foods to fill your digestive tract with healthy bacteria. This study is specifically focused on foods with resistant starch.
2) A digestive tract full of healthy bacteria blocks harmful bacteria from finding an open space, making a home and ultimately filling your body with harmful inflammation. This fights Lupus and most likely 1,000 other diseases.

[Pooka1]

Have you checked that article for bias and statistical power? The results are probably false.