Potential involvement of gut microbes in ASD  etiology has been speculated for more than a decade. Many pathogenic gram-negative bacteria contain lipopolysaccharide (LPS) in their cell walls, which can cause damage in various tissues including the brain [11]. LPS-induced inflammation in the brain increases permeability of the blood-brain barrier and facilitates an accumulation of high levels of mercury in cerebrum, which may aggravate ASD symptoms [6]. A test in rats showed that prenatal LPS exposure decreased levels of glutathione [12], which is an important antioxidant involved in heavy metal detoxification in the brain. The down-regulated synthesis of glutathione may increase the vulnerability of children to ASD and other neurologic disorders, such as Friedreich’s Ataxia [13]. Indeed, a recent pyrosequencing analysis showed that gram-negative bacteria, Desulfovibrio and Bacteroides vulgatus, were detected at higher levels in autistic children [14]. On the other hand, Clostridium, a gram positive bacterium, has also been widely studied in the context of ASD [15], [16] because it produces exotoxins and propionate. In a study on rats which was recently reported, propionate worsened ASD-like behavior [17]. In addition, Clostridium difficile produces p-cresol, which can cause depletion of glutathione [18]. Vancomycin and ampicillin, antibiotics targeting cell wall damage, significantly affect the physiology and structure of gut microbiota; especially on gram-positive bacteria such as Clostridium difficile [19]. One study showed that in a small scale clinical setting, vancomycin treatment resulted in temporary improvement of autistic symptoms in children with late-onset autism [20].

And more evidence of high levels of abnormal bacteria in Autism:            

Autism spectrum disorder (ASD) is a neurodevelopmental disorder where there is evidence of gastrointestinal (GI) disturbance in many affected individuals. Several studies have demonstrated an altered GI microbiota in children with ASD compared with controls [1-4]. Recently, Williams et al.[5] reported a significantly higher prevalence of Sutterella spp. in biopsies taken from the GI tract of ASD children with GI disturbance compared to controls with GI disturbance. Bacteria of the genus Sutterella have been identified in canine and human feces [6,7]. Sutterella wadsworthensis is noteworthy as it has been associated with some GI infections in humans [8]….. In summary, we show further evidence of changes in the gut microbiota of children with ASD, now demonstrating that fecal abundances of Sutterella and R. torques are altered…

“Studies implicate gut bacteria in autism” 

Autism, with its constellation of behavioral and cognitive symptoms, might seem to be all in the brain. But intriguing new studies suggest that some aspects of the disorder might originate in the gut.

For decades, doctors have heard anecdotal reports that children with autism have frequent gastrointestinal problems, suffering from bloating, abdominal pain, constipation, diarrhea and more.

The latest research, conducted over the past several years, probes the controversial possibility that whatever is amiss in the gut is not just a symptom of autism, but one of the causes. The work is an offshoot of mounting scientific interest in the human microbiome, the stew of bacteria that make their homes in our gastrointestinal tracts.

A new study, published 31 January in the Proceedings of the National Academy of Sciences, suggests that these microbial residents may direct brain development, ultimately shaping behavior1….A 2006 study revealed, for instance, that 70 percent of children with autism suffer from gastrointestinal problems, compared with only 28 percent of typically developing children2.

Armed with these findings, researchers began to explore whether changes in gut bacteria, rather than being mere symptoms of autism, contribute to the disorder. Anecdotal evidence suggested that might be the case — parents often reported that their children's behavior seemed to get worse when their gut symptoms were exacerbated.

………. The fecal biota of children with ASDs consistently contained different Clostridium species    than that of healthy children, as well as a statistically significant increase in clostridial species overall. The siblings of the children with ASDs exhibited intermediate levels of Clostridium species, suggesting that environmental factors and genetics may affect gut populations of these species. The researchers point out that Clostridium species produce not only enterotoxins that lead to GI problems but also neurotoxins, which they hypothesize could lead to characteristic signs of ASDs.

FMT for Non-GI Disease Encouraged by the amazing success of FMT in treating GI illness   - there is new research being done on treating non-GI diseases as well. Encouraging results have been reported in treating chronic fatigue syndrome, obesity, autism, and autoimmune diseases with FMT.

Improving the Microbiome Decreases Disease - What About Autism?

The research has been extremely positive concerning HUGE changes in the microbiome when Clostridium Difficile (C. diff.) has been treated via Fecal Transplant.  Since Autism has a significant connection to numerous and abnormally high bacteria, including Clostridia, Fecal Transplants are on the radar:

•  “Gut Feelings: Why Fecal Transplants are Gaining Ground”

 Disrupting the bodies’ internal ecosystem may do more than create a hospitable environment for C. diff. As scientists look more closely at microbiome management, hopes are high that the cure for all sorts of chronic conditions—even depression, obesity, and autism—might be tied to improving the health of our gut with a substance we are taught from childhood to shun in polite conversation. Studies are beginning to show benefits in the management of other incurable inflammatory bowel diseases such as colitis and Crohn’s disease. Positive results have also been observed in the treatment of diabetes. “There are many conditions that will likely benefit from fecal transplant,” says Sonia Michail, a pediatric gastroenterologist.

•  “Medicine’s Dirty Secret: Fecal Transplants Are the Next Big Thing in Health Care”  

At least a dozen trials are now investigating whether fecal transplants can help treat some form of inflammatory bowel disease, be it Crohn’s disease or ulcerative colitis. Another is looking into Type 2 diabetes, and one is even using lean donors to test fecal transplants on patients with metabolic syndrome. Researchers say it won’t be long before they’re joined by studies investigating whether the therapy might aid diseases like multiple sclerosis and autism.

•  “Fecal transplants dramatically improve C. difficile in kids” 

"But with ongoing inflammatory conditions, you have to do the transplant more frequently for more-modest results. There is also tremendous interest in fecal microbiota transplantation for obesity, about which we're excited but wary. We are also interested in treating abdominal symptoms in kids with autism.

•  “Fecal transplant policy and legislation”   World J Gastroenterol 2015 January 7; 21(1): 6-11

Substantial connections have also been identified between gastrointestinal health, gut microbiota, and certain neurodegenerative and neurodevelopmental disorders and those involving mood and thought[34]. The discussion surrounding autism is particularly interesting. A variety of observations linking autism to the gut microflora, such as disease onset often correlating with antimicrobial administration; increased levels of particular Clostridium species found in stool samples of autistic individuals; and the alleviation of autistic symptoms following oral vancomycin, have all supported the expansion of the traditional model of the brain-gut axis to a brain-gut-microbiota axis. Such data further allude to the vast therapeutic role of FMT (Fecal microbiota transplantation)  [34-36].

The Future – Factors to Consider, Hurdles, and Hope

•  Although standards are necessary with regard to any procedure, it is important to refrain from establishing excessive and disparate suggestions, which can have harmful consequences for patients. Guidelines are thought to be evidence-based, reliable, and precise -and therefore unbiased - but they are inherently biased in unique ways. Most guidelines are consensus reports, and as such, are influenced by authors’ convictions and their connections to external parties, including pharmaceuticals.   

•  They found the children with autism had different types of gut bacteria, and had less diversity in the numbers of different species of these bacteria, than kids without autism… The next step is to try and see if changing the populations of gut bacteria affects symptoms. “We will try fecal transplants to children with autism,” Kang said. “We will try to administer fecal material from healthy people to children with autism.”  That will require permission from several groups, including the Food and Drug Administration…….. 

•  Reduced microbiota diversity associated with C. difficile infection is reported in humans [49]-[51] and mice [52], [53]. This finding was confirmed in our study with multiple post-FMT samples collected up to one year after the procedure. Compared to healthy donors the fecal microbiota diversity of RCDI patients was reduced, as shown by rarefaction analysis of OTU counts (Fig. 2). Microbiota diversity increased significantly in post-FMT patient samples, as demonstrated by Shannon diversity index calculations… These results suggest that FMT restores the reduced microbiota diversity associated with RCDI. Furthermore, diversity increases immediately after FMT and remains stable over time.

•  HBOT [Hyperbaric Oxygen Therapy] has been used to decrease the amount of abnormal bacteria in the gut and therefore can function as an antibiotic [104]. In animal studies, HBOT was effective in reducing intestinal bacterial counts after bacteria overgrowth in the distal ileum associated with bile duct ligation [105]. It also shows bactericidal activity against many pathogenic bacteria, including Pseudomonas [106] Salmonella and Proteus, Staphylococcus [107], Mycobacterium tuberculosis [108], and anaerobic bacteria such as Clostridia [109]. Based on the fact that oxygen-dependent killing of Staphyloccus aureus by phagocytic leukocytes has been shown to increase by HBOT in animals [110], and that HBOT has also been shown to inhibit the growth of some yeast [111] and to possess virucidal activity against some enveloped viruses [112], HBOT might lead to an improvement in the dysbiosis found in some autistic patients by reducing counts of abnormal pathogens. 

•  Synthetic Poop Made in the Lab  Allen-Vercoe, who is a professor in Guelph's Department of Molecular and Cellular Biology, made her synthetic poop from purified intestinal bacteria grown in a piece of lab equipment that she and her team nicknamed the "Robo-gut".  Robo-gut essentially mimics the environment of the gut so as to produce a "super-probiotic" mix of the friendly bacteria that exist in the large intestine of healthy humans. For their proof of principle study, the researchers tested the synthetic stool on two patients with chronic C. difficile infections that were failing to respond to several rounds of antibiotics. Both patients were free of symptoms within three days of treatment, and both still tested negative for C. difficile six months later…. Allen-Vercoe hopes her synthetic poop idea can also be used to treat other gastrointestinal problems, such as inflammatory bowel disease, obesity and even autism by replacing abnormal gut microbial ecosystems with healthier versions.

•  “The Michael J. Fox Foundation For Parkinson’s Research - Gut Check on Parkinson’s: New Findings on Bacteria Levels, December 08, 2014” 

Filip Scheperjans, MD, PhD, and colleagues from the University of Helsinki, Finland examined the intestinal contents of 72 people with Parkinson’s and 72 without PD. Their research, funded by MJFF and published recently in Movement Disorders, revealed that people with Parkinson’s had lower levels of a certain bacterium and that concentrations of another bacterium varied among subgroups of those with PD with differing motor symptoms.

…..In Dr. Scheperjans’ study, the bacteria Prevotella was present at lower levels in the guts of people with Parkinson’s disease. This bacterium aids in the creation of the vitamins thiamine and folate and the maintenance of an intestinal barrier protecting against environmental toxins. This finding may therefore have implications not only for diagnosis but also for dietary adjustments or vitamin supplementation for management of PD in the future.

In people with Parkinson’s with more severe postural instability and gait difficulty, as opposed to tremor, the bacterium Enterobacteria was present at higher levels. The reasons for this association were not clear.

Studying Intestinal Bacteria Will Advance Understanding of Parkinson’s

Deciphering information from the gut could lead to earlier and more definitive diagnosis, a better understanding of how Parkinson’s progresses, and ways to separate the populations of people with differing symptoms of PD.

If researchers determine that there are specific and consistent differences in the gut, bacteria may serve as biomarkers — objective measurements to diagnose or track PD. As the gut is much more accessible than the brain and can be analyzed through stool samples, a bacterial biomarker is an attractive prospect. 

…..Additionally, we don’t know why people with Parkinson’s disease show such varied motor symptoms (gait problems versus tremor, for example) or who will get which. Bacterial differences may allow us to separate the subtypes of Parkinson’s… 

I added that last part about the Michael J. Fox Foundation as I find it pertinent and remarkable.  They are now also seeing the significance of the MICROBIOME in the development of Parkinson’s.  They are looking at bacteria and certain symptoms as their research showed it:

“Another interesting finding was that, within the PD group, abundance of Enterobacteriaceae bacteria was related to the severity of postural instability and gait difficulty (PIGD). So there was a connection between gut microbiota and the motor symptoms of our patients. Our study is the first to demonstrate alterations of microbiome composition in neurodegenerative disease. With respect to previous research it is interesting to note that reduced abundance of Prevotellaceae has been reported also in children with autism spectrum disorder and type 1 diabetes.”  

If Michael J. Fox wants to include anymore research on AUTISM, I am all for it as we need as much help as possible, plus I personally think his passion and commitment are incredible.  YEARS of wasted TIME and MONEY has kept the AUTISM EPIDEMIC rolling along. Looking at components of the microbiome as biomarkers of symptoms is brilliant and may help us see why Autism is a SPECTRUM. It may also help support the need for Fecal Transplants as well as prevention of Autism by promoting healthy microbiomes prenatally, and in infancy and childhood.

As far as hope –“ Unlike the genome, which is relatively fixed, a person's microbiome is changeable over a lifetime — and perhaps even daily.”   Also -“brain disorders, including anxiety, depression and autism, may be treated through the gut, which is a much easier target for drug delivery than the brain.” Well, that may be true and POOP may end up being the best “drug” of all.

Teresa Conrick is Contributing Editor for Age of Autism.