The Microbiome & Autism Series By Teresa Conrick: Part 2 "Does Mercury Modulate The Microbioeme?""
Note: We're sharing this series throughout the month. All roads lead to... the gut, which could explain how a certain British GI doctor became part of the autism causation maelstrom.
By Teresa Conrick
It’s a hot topic, the MICROBIOME, defined as: "the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space." I keep reading more and more research connecting the microbiome and autism.
It goes something like this, according to the research below- Mercury exposure, both environmental and via flu vaccination in a pregnant woman, can cause negative ramifications in her baby’s microbiome. The same is true for postnatal infants exposed to Thimerosal. The landscape of that microbiome loses helpful bacteria and instead we see more pathogens. The downstream effects - chronic infections, altered development of the nervous system, molecular mimicry, neuropsychiatric symptoms (tics, obsessive compulsive behaviors, perseveration and repetitive behaviors), and neurologic inflammation. Mitochondrial dysfunction, a more prevalent condition in many diagnosed with autism, seems to be part of this picture as well. Vaccines and their effect on the microbiome are also examined. Each of these studies is a puzzle piece, connecting these facts. The picture is becoming clearer:
An Immune Dysfunction of the Body Affecting the Brain
• Although the study suggested that gut bacteria could affect neurologic inflammation, how that might happen remains unclear. For the most part, Mazmanian says, the microorganisms that colonize the human gut don’t leave the intestine, but the immune cells that contact them do. He explains that, although 70% of the immune cells in the body at any one time can be found in the intestine, they circulate throughout the body, and the microbiota of the gut environment help determine how immune cells will behave elsewhere ……..Other researchers have suggested a link between the gut–brain axis and neuropsychiatric disorders such as autism, depression, and eating disorders. The gut contains microorganisms that share a structural similarity with the neuropeptides involved in regulating behavior, mood, and emotion—a phenomenon known as molecular mimicry. The body can’t tell the difference between the structure of these mimics and its own cells, so antibodies could end up attacking both, potentially altering the physiology of the gut–brain axis.12
• The human gut harbors a complex community of microbes that profoundly influence many aspects of growth and development, including development of the nervous system. Advances in high-throughput DNA sequencing methods have led to rapidly expanding knowledge about this gut microbiome.
• Autism-associated Changes in Intestinal Microbial Diversity - Maintaining sufficient bacterial richness and diversity is important for providing gut microbiota with functional redundancy, adaptability, and thus systematic robustness against environmental challenges[36]...... Rarefaction curves showed that neurotypical individuals had a higher number of observed bacterial species than autistic individuals (Figure 1A and Figure S1). ....... Taken together, these analyses suggest that the presence of autistic symptoms and their correlated GI problems are linked with reduced richness and diversity of gut microflora, which results in a decrease in microbial redundancy and alter the physiological functionality and microbial GI robustness in children with ASD.
• The reason for mitochondrial dysfunction in ASD is unknown, but the fact that only 23% of children with ASD and MD have a known mitochondrial deoxyribonucleic acid (mtDNA) abnormality suggests that MD may be acquired rather than genetic in many ASD cases…… Enteric short-chain fatty-acids, such as propionic acid (PPA),10, 11, 12, 13, 14, 15, 16, 17 which are fermentation by-products of ASD-associated enteric bacteria (that is,Clostridia, Desulfovibrio, Sutterella and Bacteroidetes), have been suggested as a possible environmental triggers in ASD.18, 19
• Furthermore, the gut microbiome emerges as a major player not only in the maturation of GIT (gastrointestinal tract) tissue and the gut brain axis but also in brain maturation, through its effect on both the immune and endocrine systems. Many toxins,toxicants, infectious agents, diet or stress, affect an individual’s gut microbiome, which may be especially sensitive during the critical developmental period. Disruption of the developing microbiome may have profound consequences on the developing gut-brain axis…..
• The bacteria that live in the human gut may play an important role in immune response to vaccines and infection by wild-type enteric organisms, according to two recent studies… Our research raises the intriguing possibility that the gut microbiota may play an important role in response to vaccines…. Metagenomics, also known as community or environmental genomics, will allow us to look at the function of the gut microbiota and how it is changing under various vaccination schedules. This research provides a fascinating window into the human microbiome, and how the bacteria in our bodies impact our health.
• Obsessive-compulsive disorder and gut microbiota dysregulation.- A hypothesis is presented wherein the root cause of OCD is proposed to be a dysfunction of the gut microbiome constituency resulting in a susceptibility to obsessional thinking…..Suggested treatment for OCD would be the directed, specie-specific (re)introduction of beneficial bacteria modifying the gut microbiome, thereby ameliorating OCD symptoms.
A Closer Look at Mercury and Thimerosal
There is much evidence that the immune system is a big player in mercury exposure. Though we hear much about the dangers of antibiotic use as the culprit for gut dysbiosis, environmental mercury and the manmade vaccine mercury, Thimerosal, appear to be involved as well. Note also the study below indicating that mercury exposure can lead to a condition where bacteria become resistant to antibiotics, even those it’s never encountered.
• As TM (Thimerosal) exposure during the postnatal phase coincided with lactation, some of the TM was delivered through the milk to the GIT and may have had an effect on the developing gut microbiome known to be sensitive to heavy metal exposure (Lapanje et al., 2007). This effect may be in part due to competition with zinc resulting in a disturbance in metallothionein function and general chelating capacity for other metals. Thus, at least part of the neonatal impact of TM/mercury could be mediated via its action on the gut microbiome.
•Increased mercury levels were detected in stools after vaccination, suggesting that the gastrointestinal tract is involved in ethylmercury elimination.
• Thousands of studies have shown that mercury affects many metabolic processes and organ systems in humans and experimental animals. Silbergeld says research by her laboratory and others indicates inorganic mercury can also impact the mucosal immune system, for instance by increasing the production of proinflammatory cytokines and serum levels of biomarkers of immune alteration related to autoimmunity.[23-26] On top of that, contact between mucosal cells of the immune system and the intestinal microbiome means each will affect the other, she says. To Silbergeld, this suggests interactions between environmental contaminants and the microbiome may be bidirectional.
• Scientists agree that re-examining environmental exposures through the lens of the microbiome is likely to yield more insights into bacterial impacts. For instance, the ability of intestinal bacteria to demethylate methyl-mercury[19] is important because the process could result in unexpected exposure to toxic inorganic mercury.
• Antibiotic-treated rats given [203Hg]-labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results suppport the hypothesis that the metabolism of methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/kg . day for 6 days, four of five of those given antibiotics developed neurological symptoms of toxicity.
• Summers says bacterial exposure to metals such as mercury can contribute to antimicrobial resistance because many transferrable plasmids carry genes for multiple types resistance. In other words, in the process of developing metal resistance, a bacterium may also become resistant to an antibiotic it hasn’t even encountered.
• It has been suggested that the environmental load of mercury, including that released from amalgam fillings, may promote and maintain antimicrobial resistance together with mercury resistance in human normal flora (20). The threat of pathogens acquiring this resistance is always present; one example is the transfer of penicillin resistance genes from oral streptococci to Streptococcus pneumoniae (3).
• …..raising the question of whether changes in the human chromatin, induced by mercury, in a parental generation could allow adaptation of their descendants to mercury……..in Australia the mercury sensitivity of paternal grandparents who had pink disease as infants, affected their grandchildren [autism][32]…… In humans the microbiome is also closely linked to physiology and disease. Mercury resistant bacteria have been well recognized [30]. Since one route of entry of mercury in humans is through the gut, the microbiome might be the first to encounter the toxin and the bacteria adapt to increasing levels of ingested mercury……
Not Genes
The constant parade of genetic research over decades has given nothing of value. NIH, National Institutes of Health though, is spending millions on the Human Microbiome Project. There are hints that autism is included but to what extent? This from NIH Director, Francis S. Collins: “Realizing that the immune system interacts closely with normal microbes, Hsiao is now focused on how gut bacteria influence immunity, brain function, and behaviors in mouse models of neurodevelopmental disorders. In a just-published study, she reveals that when mice that display core symptoms of autism spectrum disorder are given bacteria-laden treatments called probiotics, many of the mice’s behavioral abnormalities disappear [6].” It’s a step in the right direction yet their culprit in all of this is not mercury or Thimerosal. It is mothers getting sick during pregnancy, “maternal immune activation.” There has been little research in the use of flu shots and Thimerosal with pregnant women and the development of activating the immune system. It is an area that needs more research. So here are studies showing how it is the microbiome, not genes, that will lead the way in helping so many stricken with these symptoms:
• That veil is only very recently being lifted with respect to a potential role for autoimmunity in neuropsychiatric disorders. This shift has occurred as evidence accumulates to support the idea that dysregulated cross-talk between the brain and the immune system is an important contributor to the pathogenesis of conditions as diverse as schizophrenia, mood disorders, autism spectrum disorders (ASDs), obsessive-compulsive disorder (OCD), Tourette syndrome and other tic disorders, attention-deficit hyperactivity disorder (ADHD), anorexia nervosa, narcolepsy, posttraumatic stress disorder and myalgic encephalomyelitis/chronic fatigue syndrome (CFS).[4,5] In addition, intriguing new evidence lends support to the possibility that not only the microbes associated with infectious episodes but also the bacteria of the gut microbiome can foster the production of brain-reactive autoantibodies, and that these microbe-induced antibodies provide the critical link between infection and neuropsychiatric disorders.
• ….Eventually, as more pathogens are incorporated into the microbiome and levels of dysbiosis increase, people begin to present with symptoms characteristic of an autoimmune or inflammatory diagnosis......There is increasing evidence that autoimmune diseases run in families due to the sharing of common microbes.... The microbiome a child develops is a direct reflection of those harbored by the mother and close relatives. Microbes are introduced by a multitude of sources including the placenta, sperm,egg, breast milk, and vaginal canal.[37] …. Autoimmune diseases are more likely passed in families due to inheritance of the familial microbiome than inheritance of Mendelian genetic abnormalities.”
• Lisa Helbling Chadwick, the NIEHS liaison for the Human Microbiome Project, says the institute is increasing its focus on the impact of microbiomes on toxicology. "One thing we are really interested in at NIEHS is understanding how individuals respond differently to exposures, what makes one person more susceptible to adverse health outcomes from an exposure than another," she says. "Genetics only partially explains this." Birnbaum adds, "We recognize the enormous implications of the growing awareness of interactions between chemical exposures and the microbiome, and we have begun exploring these issues."
• Existing therapies targeting the gut microbiome include diet, antibiotics, and probiotics. Dietary restriction, including the removal of dairy casein-containing products, wheat and gluten sources, sugar, chocolate, preservatives, and food coloring have all been found to be therapeutic in autism….. . Gastrointestinal problems in autism appear to respond to antimicrobial agents. Treatments targeting Candida, and probiotics have been used to reduce disbiosis and control gut permeability (Kidd, 2002). Other strategies include the removal of heavy metals (including mercury) by chelation and sulfur-sulphydryl repletion. Supplementation with dimethylglycine, vitamin B6, magnesium, vitamin B3, C, folic acid, calcium and zinc, cod liver, digestive enzymes, all appear to be beneficial in a number of autistic children (Kidd, 2002). Immune therapies, including pentoxifyllin, immunoglobulin, transfer factors and colostrums appear to work in a limited number of cases.
• Increasing evidence indicates that the complex microbial ecosystem of the human intestine plays a critical role in protecting the host against disease. This review discusses gut dysbiosis (here defined as a state of imbalance in the gut microbial ecosystem, including overgrowth of some organisms and loss of others) as the foundation for several diseases, and the applicability of refined microbial ecosystem replacement therapies as a future treatment modality..... 'Microbial Ecosystem Therapeutics' (MET) would entail replacing a dysfunctional, damaged ecosystem with a fully developed and healthy ecosystem of 'native' intestinal bacteria. Its application in treating Clostridium difficile infection is discussed and possible applications to other diseases such as ulcerative colitis, obesity, necrotising enterocolitis, and regressive-type autism are reviewed.
Note that the above study refers to "regressive-type" autism as a disease. I have watched my own daughter suffer for years -- infections, pain, neuropsychiatric symptoms related to PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and an autoimmune diagnosis shown by antinuclear antibodies. Since 1938, those with the symptoms called “autism” have been put on a spectrum, from low functioning to high functioning. It is very possible that their functioning had everything to do with a dysfunctional microbiome.
Holly;
thttp://www.nature.com/news/bacteria-from-lean-cage-mates-help-mice-stay-slim-1.13693
This is from the magazine "Nature" you can get a handle on the researcher's name.
Germ Free mice - they have learned certian birth procedures to produce them.
Have you had time to watch the TV show about following people and documenting on film - the morbid obese? THe doctor on that show suggest Low carb diet. That helps change the microbiome.
Which is discussed on the U tubes recorded about the human Microbiome project - of a meeting held by the NIH - I think back in the early summer of 2013.
But more helpful was the microbiome meeting held in Arkansas for autism -- there was discussions of fecal transplants, robo - guts, yogurt - fermented foods. These are on U tubes too but I could not get them on aol - I had to go to internet explorer to see them.
And of course the most trusted Pub-med -- here is a two of many:
Pub med : http://www.ncbi.nlm.nih.gov/pubmed/17183312
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104783/
Posted by: Benedetta |
Posted by: Benedetta | December 17, 2014 at 09:57 AM
Hi Holly,
Thanks for reading. Here are some sources and best of luck:
http://www.microbiomejournal.com/content/1/1/24
"Similarly, obesity and anorexia are also associated with the alteration of the relative composition of some gut microbes [27,37]. Turnbaugh et al. identified changes in the gut microbiome as an additional factor contributing to the pathophysiology of obesity [38]. In obese microbiomes an enriched gene set for increased capacity for energy harvest from various sources was observed [38]. On the opposite spectrum of obesity is anorexia. Individuals with anorexia are known to harbor an altered microbiome where Methanobrevibacter smthii is dominant in the gut of anorexic individuals [37]."
Molecular Origins Of Eating Disorders Found In Gut Microbe
http://www.neomatica.com/2014/10/08/molecular-origins-eating-disorders-found-gut-microbe/
"Now researchers at the French Institute of Health and Medical Research and the University of Rouen in France have found strong evidence that a protein made by intestinal bacteria are a causative agent for the disorders. Specifically, antibodies made by the host against this protein cross-react with a mammalian satiety hormone. The severity of symptoms in ED patients was also found to correlate with levels of the neutralizing antibodies. The researchers believe that this understanding will ultimately lead to a chemical therapeutic strategies to correct eating disorders."
http://www.jci.org/articles/view/58109
http://www.newrepublic.com/article/116071/microbe-transplant-research-gut-bacteria-could-treat-autism-obesity
"Lean mice have been made obese simply by giving them the gut flora of obese mice. And, in a remarkable study published in September, gut flora taken from human twins where one is obese and one is lean affected the corpulence of the mice that received them. Those that received the microbiome of the fat twin became fat, and the ones that got the lean twin’s bacteria became lean. Body shape is, to a certain degree, transmissible."
Anorexia / bulimia: a bacterial protein implicated
http://www.translationalmicrobiome.org/news/anorexia-bulimia-a-bacterial-protein-implicated/
"Eating disorders (ED) such as anorexia nervosa, bulimia, and binge eating disorder affect approximately 5-10% of the general population, but the biological mechanisms involved are unknown. Researchers at Inserm Unit 1073, “Nutrition, inflammation and dysfunction of the gut-brain axis” (Inserm/University of Rouen) have demonstrated the involvement of a protein produced by some intestinal bacteria that may be the source of these disorders. Antibodies produced by the body against this protein also react with the main satiety hormone, which is similar in structure. According to the researchers, it may ultimately be possible to correct this mechanism that causes variations in food intake.
These results are published in the journal Translational Psychiatry, in the online issue of 7 October 2014.See the video of the discovery (English subtitles)"
"Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders"
http://www.nature.com/tp/journal/v4/n10/full/tp201498a.html
The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs.
Posted by: To Holly | December 17, 2014 at 09:55 AM
You mention that other researchers have suggested links between gut-brain circuitry and eating disorders. Can you give the links? I'm a psychologist who is working with people with eating disorders that seem to have resulted from digestive issues, meaning that the psychiatric issues seem to have been drawn towards eating disorders because of the discomfort from eating when the digestion is disturbed. I do not know of any sources though for this in the research and I'm trying to convince treatment centers to respond more appropriately.
Thank you!
Posted by: Holly Timberlake, PhD | December 17, 2014 at 08:59 AM
How many times have we heard some one say in a fatalistic way; Well cancer just runs in our family -- implying it is the genes and there is nothing they can do.
My friend when I was telling her about delaying the DTP would reduce incidences of asthma - responded by saying asthma runs in the family and started naming names.
Or how many times have we heard that sugar (meanind diabetes) is in our family.
So I loved this:
• ….Eventually, as more pathogens are incorporated into the microbiome and levels of dysbiosis increase, people begin to present with symptoms characteristic of an autoimmune or inflammatory diagnosis......There is increasing evidence that autoimmune diseases run in families due to the sharing of common microbes.... The microbiome a child develops is a direct reflection of those harbored by the mother and close relatives. Microbes are introduced by a multitude of sources including the placenta, sperm,egg, breast milk, and vaginal canal.[37] …. Autoimmune diseases are more likely passed in families due to inheritance of the familial microbiome than inheritance of Mendelian genetic abnormalities.”
Oh, by the way -- thyroid disease does not run in my family -- never heard of it-- I have it.
And untill this generation in our family neither did autism.
And for that matter diabetis is hardly a disease that has been around either.
Hmmm and cancer and astma -- too much of that and there would hardly be 7.3 billion people on the planet. Which by the way is not as many as we think -- since we could all fit into the city limits of Los Angeles
It does not take much to go from a very successful organism in just a few generations to a struggeling organism.
That is biology 101.
Posted by: Benedetta | December 07, 2014 at 12:24 PM