Chronic Fatigue and Inflammation

I’ve written before about the times years back when people with chronic fatigue syndrome were vilified as “lazy.” In that post, I talked about recent research looking at alterations in the gut bacteria as being associated with the disease.

Yesterday, the big health news [i]  came out of Stanford University School of Medicine identifying 17 cytokines (13 of which are inflammatory in nature) whose levels in the blood correlate with the disease severity.  What’s really great about this is that it not only provides a potential easy blood test to identify the illness, but it also proves that the disease itself is the result of high levels of inflammation.

Great quote from one of the researchers: “’I have seen the horrors of this disease, multiplied by hundreds of patients…It’s been observed and talked about for 35 years now, sometimes with the onus of being described as a psychological condition. But chronic fatigue syndrome is by no means a figment of the imagination. This is real.”

One thing I thought particularly interesting about their research:

“One of the cytokines whose levels corresponded to disease severity, leptin, is secreted by fat tissue. Best known as a satiety reporter that tells the brain when somebody’s stomach is full, leptin is also an active pro-inflammatory substance. Generally, leptin is more abundant in women’s blood than in men’s, which could throw light on why more women than men have ME/CFS.”

Interestingly, leptin apparently has a role in regulating the bacterial microbiome.  “A new study in this issue of Endocrinology by Rajala et al (19) indicates that leptin is a key player in regulating both antimicrobial peptides and microbiota composition.”[ii]  What’s unknown yet is whether leptin regulates antimicrobial peptides, which in turn alter microbiome composition or whether it directly signals the bacteria of the gut.

It all kind of ties in together:  the bacterial microbiome, high levels of leptin, chronic fatigue syndrome.  Where I a gambler, I’d put my money on microbiome alterations being a the heart of the whole thing!

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[i] https://www.eurekalert.org/pub_releases/2017-07/sumc-sri072617.php

[ii] Sandoval, D. Old dog, new trick: a direct role for leptin in regulating microbiota composition. Endocrinology. 2014;155(3):653-655.

More on Our Missing Macrobiome

Dr. Jamie Lorimer is a researcher at Oxford University, who focuses “…in particular on the rise of helminthic and other forms of biotherapy for tackling autoimmune and allergic disease.”[i]  I read a fascinating paper[ii] by him yesterday that looked at helminths and health in relation to geography.  The paper is a nice follow up to my last post, where I describe how different organisms can affect health differently depending on environment.

The main point of the paper is that helminths (Dr. Lorimer uses hookworm for his specific example) can either be parasitic (as in the case of excessive loads, in poor, undeveloped countries…and under these circumstances of excess, are pathogenic); ghosts (where, in industrialized world, we’ve eradicated them – and their absence has become pathogenic); or mutualists (where, in small, therapeutic doses, they can benefit their hosts).

Again, the same organism, under different circumstances, can affect health in different ways.

Dr. Lorimer mentions how our discovery of germs led to a frenzy of eradication. “…few microbes = better places.”  However, as he points out, “Hookworms were eradicated from North America and Europe at the start of the 20th century through the development of antimicrobial drugs and improvements in sanitation.  The absence of hookworms has been implicated in the rise of dysbiosis.  The demise of the ‘old friends’ is understood to imbalance the immune system, turning it against self and generating a range of autoimmune, allergic and inflammatory diseases.”  That is, absence is just as pathogenic as excess.

Thus, with helminths having become ghosts in the industrialized world, “Interventions like flush toilets, antibiotics and C-sections, which have been central to Western narratives of civilisation and development, have been recast as potentially pathological.”

(Hmm.  I’ll keep my pathological toilet, thank you very much!)

My favorite quote though is this:  “The story here is of health and safety going too far.  An excessive desire to minimize risk and modulate microbial infection intensity creates a model of biosecurity that is prone to autoimmunity: ‘a self-protective syndrome whose attempts to exclude difference are ultimately self-destructive.’”

Completely coincidentally, earlier today, as I was starting to write this post, an article popped up in my inbox from one of my automated searches:  One in 20 adolescents in Australia have food allergy: study.[iii]

 “One in 20 adolescents in Australia aged 10 to 14 have a food allergy….’There has been an increase in prevalence of allergies in Australia, one in 10 babies aged 12 months now have a food allergy’ food allergy expert and chief executive officer of Anaphylaxis Australia, Maria Said explained…’Have we created environments that are too clean so our immune system comes unstuck with something as natural as a food protein’ the expert wondered.”

What I wonder is, what does it take for the scientific community to accept something as a truth?

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[i] https://www.hertford.ox.ac.uk/about/people/dr-jamie-lorimer-0

[ii] Lorimer, J. Parasites, ghosts and mutualists:  a relational geography of  microbes for global health. Rogyal Geographical Society. 2017. Doi:10.1111/tran.12189.

[iii] http://news.xinhuanet.com/english/2017-07/27/c_136477096.htm

Immune Tolerance: A Great New Study

The biome buzz these past few days was on research that shows that the same bacteria can cause different immune responses in different gut environments.[i]  For many years, Helicobactor bacteria have been associated with stomach ulcers.  It was always strange though, in that, most people (two-thirds of the world’s population, according to WebMD[ii]) have the species as a normal part of the biome.  Why then in some does it become problematic?

In this study, when it was introduced into healthy mice in a mostly germ-free environment, the immune system tolerated its presence just fine.  However, when it was introduced into mice that are genetically prone to developing colitis, the immune system regarded it as a threat and gut inflammation worsened.

“The study suggests that Helicobacter and similar bacteria labeled as “bad” may, in fact, be neutral or even beneficial, depending on the health of the individual. A person’s level of stress, poor diet or genetics all may influence the good or bad nature of gut bacteria, the scientists said.”

Immune tolerance is a key concept:  the idea that our bodies should be able to differentiate pathogens from the benign.  With our depleted biomes (not just the bacteria, of course, but the mycobiome, the macrobiome, etc), we’ve lost that tolerance. Really, you do have to wonder what would happen were these scientists to inoculate the mice prone to colitis with helminths, wait a few weeks, and see if the Helicobactor still caused increased inflammation.  Can increasing immune tolerance, via biome enrichment, counteract that tendency to hyper-react to neutral, or even benign, bacteria?

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[i] https://www.livescience.com/59900-gut-environment-affects-whether-bacteria-are-good-or-bad.html

[ii] http://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori#1

The Elephant in the Biome

There’s no denying that the microbiome is the hottest thing in medicine these days.  In looking through the medical news and research, I notice daily that the trending, hip, cool and cutting-edge media, like the Huffington Post, are all saying, “The microbiome is “in.”[i]

My blog and I are so totally the avant-garde!

What continually strikes me though is that all these articles focus exclusively on the importance of the bacterial microbiome, even when the article itself alludes to the macro.

For example, this week, Northwestern University’s newsletter contained an article called “Germs at Four, Less Inflammation at Forty,”[ii] about the importance of exposing the infant’s developing immune system to a wide variety of pathogens to train it so that in the future, it can properly differentiate good from bad.  “But exposure to germs, especially in early life, educates our immune system and helps it regulate inflammation more effectively.”

The article describes recent research that looked at babies growing up in remote, non-industrialized societies and concluded that, “…babies surrounded by germs grow up to have lower levels of inflammation in later life.”  And right in the opening section of the piece, one of the researchers is quoted as saying, “Prior research had shown that being exposed to certain types of germs and parasites during early life might, somewhat paradoxically, reduce one’s risk of suffering from allergy later in childhood and adulthood.”   The word parasite (or any related word, like helminth) is not mentioned again.

Helminths are the elephant in the room.  Everyone knows they’re there but no one wants to talk about them.

(They are not sexy…(yet)!  Of course, by the time I get through with them….)

I do wonder how much longer researchers (and too many science writers) can pretend the helminthic elephant isn’t there.  We did not evolve with only a bacterial microbiome. Sheesh! The human body is a complex ecosystem consisting of way more than just bacteria.

What disturbs me most of all are sentences like this (which I see in some form, in almost everything I read):  “Maybe we can develop something analogous to a vaccine to give children a safe dose of germs at key moments of immune development in the first six months to two years of life…”  Wait…what?!

In my head, I hear the voice of my friend, William Parker (a researcher at Duke University, who studies the immunological effects of helminths among other things), saying – as he did in an article in Undark[iii] last year, “’It’s like a bunch of scientists standing around looking at a fish out of water, waiting till he gets sick, and then we’re going to figure out how we’re going to fix him with chemicals,’ Parker says. ‘It doesn’t make any sense, but that’s the dark side of modern medicine, right there. Because we’re not looking for water to put in the fish tank.’”

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[i] http://www.huffingtonpost.com/entry/what-happened-to-our-microbiomes_us_596ebc28e4b05561da5a5bc1

[ii] https://news.northwestern.edu/stories/2017/july/germs-at-four-less-inflammation-at-forty/

[iii] https://undark.org/article/helminths-ibs-worm-parasite-auto-immune/

Helminths, Our Genes and Alzheimer’s – Mind Blowing!

One of the most interesting articles[i] I’ve read in a long time appeared in the New York Times this past weekend.  I highly recommend you take the time to read the whole thing but in case you’re pressed for time, here’s a quick synopsis:

The ApoE4 gene is known as the Alzheimer’s gene.  Those of us in industrialized societies who carry 2 copies are more than 10X as likely to develop the disease.  Strangely enough though, those in pre-industrialized societies perform BETTER cognitively if they carry 2 copies of the gene.  How is this possible?

Not many of us have 2 copies of the gene, and only about ¼ of us have 1 copy.  However, it was ubiquitous in our ancestors.  Why?  Likely, it was important in the development of our “big energy-hungry brains.”  Researchers believe that the ApoE4 gene is crucial somehow in defending our brains from pathogenic invaders.

So what is the difference between those in pre-industrial societies – where the ApoE4 gene provides major neuroprotection – and those of us in the industrialized world, where it hugely increases our risk of dementia?

Helminths.

Dr. Ben Trumble, of Arizona State, found that in a group of Bolivian natives (who still live in a pre-industrialized society), “…those with infections were more likely to maintain their mental fitness if they carried one or two copies of the ApoE4 gene; for them, the “Alzheimer’s gene” provided an advantage. For the minority who’d managed to elude parasitic infection, however, the opposite was true, and the ApoE4 gene was connected with cognitive decline, just as it is for people in industrialized countries.”

How amazing is that?!!!!

The likely culprit has to do with astrocytes, cells that support neurons and keep them healthy.  Recent research out of Stanford shows that these cells can flip into “killer mode” and start to destroy the very cells they’re supposed to protect.  “Nowadays, since most of us live in more sterile environments, this army in our brain is no longer busy fighting pathogens, and so it responds instead — often far too vigorously — to the amyloid plaques and tangles that are a part of normal aging.”

That sounds a whole lot like it’s saying that without helminths, autoimmune activity develops in the brain, doesn’t it?

Of course the scientists in this article say that we should not use helminths.  After all, there is a lot we don’t know, etc. etc. etc..  (And, not to sound too cynical but – they’d also like to develop “designer parasites” which they can patent and sell for billions of dollars.)

On the other hand…hmmm…I can possibly protect my brain from dementia now and not wait until someone has developed a pharmaceutical in a few decades?  To me, that’s not a question.

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[i] https://www.nytimes.com/2017/07/14/opinion/sunday/alzheimers-cure-south-america.html?smprod=nytcore-ipad&smid=nytcore-ipad-share

Bits and Pieces…

I’m really tired today and my brain is definitely even weirder than usual. (I was up about 10 times last night, and when I’d doze off, I kept dreaming of ways to fix the newest Star Wars movie (Rogue One) which we watched last night.  (Yeah –  just like the 3 prequels and Episode 7, it just didn’t cut it for me.) My brain’s solution:  insert Tyrion Lannister into the movie.  Honestly, I can’t tell you how much more enjoyable the movie was with him in it!)

So, this post is potluck.  I’ve read all kinds of interesting bits and pieces this week and since I’m having trouble concentrating, I figured, I’d better stick to simplicity and short paragraphs!

  1. Did you know   that 150 million people in Europe now suffer from allergies and that number is expected to increase to half the European population by 2025?[i]  Holy cow!
  2. New research[ii] was presented at the FEMS-2017 conference (for microbiologists) that shows that bacteriophages – which are viruses that infect bacteria – may alter the gut biome and cause increased gut permeability (leaky gut).  This could have tremendous relevance for illnesses like autism, Alzheimer’s, diabetes, heart disease and autoimmune illnesses.  (I’m sure Parkinson’s as well!)  That is, essentially, infection of the microbiome can lead to human disease.  (Of course, since these viruses have been present in all mammals for all of our evolutionary history, you do have to wonder why now they’re suddenly causing all these inflammatory illnesses.  Is it that we already have such depleted and altered biomes that this further depletion has become problematic?  Or is it that the species of bacteria we do have are more susceptible to these bacteriophages? Just hypothesizing for a moment…)
  3. I want to make sure you didn’t miss the research[iii] out of the University of Chicago this week that showed that antibiotic treatment in mice during pregnancy and early nursing period makes the pups more susceptible to developing inflammatory bowel disease later in life. As the antibiotic treatment did not cause the mothers to develop IBD, the researchers conclude that it’s all in the timing: “…the timing of antibiotic exposure is crucial, especially during the early developmental period after birth when the immune system is undergoing maturation.”   All I keep thinking about is my son being hospitalized at 36 hours old and pumped full of antibiotics for 5 days…who then went on to develop both IBD and autism.  (Don’t get me started.)

Ok…was I coherent?

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[i] [i] https://www.allergyuk.org/information-and-advice/statistics

[ii] http://www.digitaljournal.com/pr/3410641

[iii] https://www.sciencedaily.com/releases/2017/07/170711125702.htm

The Mycobiome, the Bacterial Microbiome and Inflammatory Bowel Disease

An interesting piece of research[i] was present last week at a conference in Chicago.  Firstly, as I’ve talked about before on this blog, it’s important to remember that humans’ incredibly complex natural ecosystems have a mycobiome (native yeast population), just as we have a bacterial microbiome and should have a macrobiome, and without a doubt, each affects the other.

In this study, researchers induced colitis in mice and then infected a subset with C. tropicalis, which is a normal part of the human mycobiome.  (Apparently, it’s the second most common yeast in humans, after Candida albicans.)  The mice in this subset had markedly worse Crohn’s disease symptoms.  What makes this research even more interesting is that the mice infected with the C. tropicalis had much higher levels of proteobacteria (like types of E.coli) in their intestines – a bacteria already associated with the development of IBD.   That is, a yeast induced dysbiosis and this, in turn, caused much higher levels of proinflammatory cytokines.  They also had more severe visual signs of swelling.

“This confirmed that the presence and the abundance of fungi in the intestine have the ability to modify the bacteria living in our intestine, leading to a dysbiosis which will eventually trigger an inflammatory syndrome.”

The authors suggest that using anti-fungal medications may make a positive difference, therefore, in IBD.

What’s a really interesting thought is that we’ve known for decades that using antibiotics can lead to yeast infections.  Each keeps the other in check.  Is it not just the direct negative effect on the gut bacteria that are problematic, but also, the fact that after a round of antibiotics, yeast levels go up?  So, I got to wondering if there are any statistics on the relationship of the development of IBD to antibiotics use.  And sure enough, I found this in an article[ii] from 2013:

“We found an increased association between prior antibiotic use and an IBD diagnosis in adults just as we had in children. We found that the greater the antibiotic use, the stronger the association between antibiotic use and an IBD diagnosis.”

I also found, in this article, more than I bargained for:

“We questioned whether antibiotic use plays a role in the development of pediatric IBD. Of particular interest was whether antibiotic use in a child’s first year of life is because the gut microbiome—as far as our current understanding goes—is like a fingerprint. The gut microbiome begins to establish itself when we are young children of, maybe, 1 year or so of age. The gut microbiome is developing in that first year of life, but after this time, it stays pretty constant. Events, such as infections, may occur in that first year of life that impact the gut microbiome in such a way that some permanent changes occur….We found that children who had an IBD diagnosis were about 3 times more likely than children without an IBD diagnosis to have received antibiotics in the first year of life.”

Well, as the parent of a child given copious amounts of antibiotics starting on his 2 day of life, who then went on to develop both autism and IBD, that just made my day.

Not.

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[i] https://www.specialtypharmacytimes.com/news/intestinal-fungus-may-trigger-gut-inflammation-in-crohns-disease

[ii] Bernstein, CN. Antibiotic use and the risk of Crohn’s disease.  Gastroenterology & Hepatology. 2013; 9(6):393-395.

A Big Time Parkinson’s Brood

As I sit here this morning, the rain is heaving down outside.  It is dark and dismal and reminds me of my trip to the UK last week.  (Except that it’s 30 degrees warmer here!)

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This of course brought to mind some of the events of that trip…which included finding out that yet another friend, also around 50 years old, has just been diagnosed with Parkinson’s.  That’s already the 3rd for me, diagnosed with what used to be called an old man’s disease.  (Men are more likely to develop Parkinson’s than women.)

Ironically, over dinner and before he told me the news, I’d commented that I have been very upset lately, watching all my friends – all 50ish, give or take a few years either way – become sick.  For the women, it’s mainly reproductive cancers and Hashimoto’s (autoimmune thyroid disease).  For the men, it’s Parkinson’s and IBD.  The list also includes severe allergies, cardiovascular illnesses, migraines, other digestive illnesses, depression, and anxiety issues.

I told my friend that if he were going to get the diagnosis of Parkinson’s, this was the week to do it.  So said his neurologist, funnily enough.  As you all know if you’ve been reading my blog regularly, an astounding number of seminal papers have been published recently.

I looked up the rates of Parkinson’s, curious to see if it too is increasing in frequency, like so many other inflammatory illnesses.  According to the Parkinson’s Disease Foundation[i], “As many as one million Americans live with Parkinson’s disease…” and “Approximately 60,000 Americans are diagnosed with Parkinson’s disease each year…”  Holy cow.  Almost exactly a year ago, an article[ii] was published in JAMA  Neurology that states that yes, the incidence between 1976 and 2005 more than doubled in older men. (It does not, however, state whether or not the incidence is increasing in younger men too, only that it’s more common in older than younger.)  And their suggested cause of this enormous increase?  The decrease in smoking rates.  Apparently, smoking is associated with a reduced risk of Parkinson’s.  I’m sure I don’t need to state the obvious here…but I will anyway, ‘cause I can never resist a good bit of sarcasm to amuse myself.  Is the medical solution then to the increased rate of Parkinson’s disease to start encouraging smoking?! Because that’s going to work out well for everyone.

What with the fact that in the last 3 months, research has pretty clearly suggested that Parkinson’s starts with a negative alteration of the gut biome; that this chronic “infection” leads to increased production and eventual aggregation and distortion (folding) of the immune protein, alpha-synuclein…which then travels from the gut to the brain via nerves, causing an autoimmune response in the brain leading to the destruction of dopamine producing cells…well, once again, doesn’t common sense dictate that working on the health of the gut biome would at least help…and certainly not hurt?

I mean, call me crazy but….

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[i] http://www.pdf.org/parkinson_statistics

[ii] Savica, Rodolfo, et. al.  Time Trends in the Incidence of Parkinson’s Disease.  JAMA Neurology. 2016;73(8):981-989.

Your Brain on Intestinal Bacteria

I got back from the UK on Sunday night.  I had a wonderful time talking helminths with practitioners from all over the world at the International Congress on Naturopathic Medicine…and of course, having a pint in the pub!

IMG_20170629_175403748_HDR

With one of my BFFs, Marc.  (And yeah, ok – I’m only having a half pint.  I’m a lightweight!)

 

Now I feel overwhelmed in that I have so much to catch you all up on, in terms of biome research. Honestly, who’d have thought even a few years ago that so much could happen in just one week in the world of our intestinal old friends!

So, to pick one of the high points:

A new study[i] was just published looking at how the composition of the gut microbiota affects human emotions.  Researchers at the University of California took fecal samples from 40 healthy women between 18 and 55 years old.  They noted that the microbiota composition fell into 2 distinct groupings, with one have more Bacteroides species and the other having more Prevotella species.  The women were giving MRIs to examine their emotional responses while looking at pictures designed to provoke positive, negative or neutral emotions.

The group with more Bacteroids had thicker grey matter in their frontal cortex, which is the area of the brain that processes complex information.  They also had a larger hippocampus, which is your memory center.  (It’s the area of the brain most affected in Alzheimer’s.)  The women with more Prevotella had a smaller frontal cortex and hippocampus, and showed greater connections between emotional, attentional and sensory regions of the brain. This latter group reported “greater levels of anxiety, distress and irritability when looking at negative images.”[ii]

The authors of the paper point out that the hippocampus regulates emotions, so with it being smaller in the Prevotella group, they may have less ability to contain emotions:  “Reduced hippocampal engagement to negative imagery may be associated with increased emotional arousal.”

The implications of this are obviously tremendous, especially when you consider the staggering rates of “mental illness” in the industrialized world, ranging from depression and anxiety disorders to autism.  This is possibly the first time that gut microbiota have been proven to affect not only the physical composition of the brain, but how humans think and feel.  Amazing!

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[i] Tillisch, K, et. al. Brain structure and response to emotional stimuli as related to gut microbial profiles in healthy women.  Psychosomatic Medicine. 2017. doi: 10.1097/PSY.0000000000000493

[ii] http://www.huffingtonpost.co.uk/entry/gut-bacteria-really-do-affect-your-emotions_uk_595b6434e4b05c37bb7ffeda

More Exciting News on Parkinson’s Research

Well, it looks like researchers have finally cracked the Parkinson’s/autoimmune puzzle.  For years, it’s been suspected that there was an autoimmune component.  Now, finally, it’s confirmed.

Says Dr. David Sulzer at Columbia University, one of the lead researchers on the study[i] just published in Nature, “Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson’s, can activate the T cells involved in autoimmune attacks.”

This study found that “T cells can be tricked into thinking dopamine neurons are foreign by the buildup of damaged alpha-synuclein proteins.”

Remember that just a week ago or so, research[ii] came out of Duke University showing that the damaged alpha-synuclein protein found in both Parkinson’s and Alzheimer’s, seems to originate in the endocrine cells of the gut.  Scientists were amazed to find that the gut endocrine system establish connection with nerves.  “…the endocrine cells – which are not nerves…are able to communicate directly with the nervous system and brain.”

The question then becomes, of course, will treating Parkinson’s with anti-inflammatory pharmaceuticals and/or natural treatments make a difference?  Can the deterioration be halted or even reversed?

In other news, I probably will miss a week of posting on my blog as I’m leaving for the UK on Sunday night.  On Tuesday I may be filmed by a major network news team (ugh! nerves!) and on  Wednesday, I’ll be spending the afternoon with a reporter from The New Scientist talking helminths.  I’ll also be attending a big, international conference on naturopathic medicine. I will write all about my adventures when I get back!

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[i] https://www.sciencedaily.com/releases/2017/06/170621132904.htm

[ii] https://www.sciencedaily.com/releases/2017/06/170615100616.htm