I have written a more general post about the connection between autism and problems in the gut, but want to focus specifically on the imbalanced microflora that is such a major part of this. Many of the symptoms of autism can result directly from the toxins and metabolites produced by the overgrowth of pathogens, and other symptoms can result indirectly from these imbalances. These symptoms can include sensory issues such as sensitivity to light and sound, obsessive compulsive disorder or tendencies, stimming, self-injurious behavior, aggression, sleep problems, pickiness and food aversions, hyperactivity, anger and rage, other mood issues, rigidity, speech problems, difficulty with processing language, allergies, altered sensitivity to pain, and many more. These imbalances can lead to or worsen common biological conditions in autism such as mitochondrial dysfunction, high histamine levels, high oxalate levels, leaky gut and IgG food allergies, and possibly even Pyroluria.
A number of studies have found that the gut flora of people with autism is quite different than that of healthy controls. One recent study, Pyrosequencing study of fecal microflora of autistic and control children looked at the bacterial composition of microflora in 33 children with autism who have gastrointestinal symptoms compared to controls and found many significant differences, including:
"At the phylum level, Bacteroidetes and Firmicutes showed the most difference between groups of varying severities of autism. Bacteroidetes was found at high levels in the severely autistic group, while Firmicutes were more predominant in the control group. Smaller, but significant, differences also occurred in the Actinobacterium and Proteobacterium phyla. Desulfovibrio species and Bacteroides vulgatus are present in significantly higher numbers in stools of severely autistic children than in controls."
Desulfovibrio is a bacteria that causes problems with the metabolism of sulfur, which is a very common problem for people with autism. It seems that the water supply may be one source of this bacteria. If that is where it is coming from, then it would seem that colonization with this bacteria would be the result of an immune deficiency?
Some other recent studies have found that children with autism who also had gastrointestinal complaints had high levels of certain bacteria in gut biopsies, called Sutterella, that was not found in control subjects who did not have autism but did have GI complaints.
Application of Novel PCR-Based Methods for Detection, Quantitation, and Phylogenetic Characterization of Sutterella Species in Intestinal Biopsy Samples from Children with Autism and Gastrointestinal Disturbances
"Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella
species and GI disturbances in children with autism. These findings
elevate this little-recognized bacterium to the forefront by
demonstrating that Sutterella is a major component of the
microbiota in over half of children with autism and gastrointestinal
dysfunction (AUT-GI) and is absent in children with only
gastrointestinal dysfunction (Control-GI) evaluated in this study."
"In a previous study, we showed that a complex interplay exists between human intestinal gene expression for disaccharidases and hexose transporters and compositional differences in the mucoepithelial microbiota of children with autism and gastrointestinal disease (AUT-GI children) compared to children with GI disease but typical neurological status (Control-GI children). Significant compositional changes in Bacteroidetes, Firmicutes/Bacteroidetes ratios, and Betaproteobacteria in AUT-GI intestinal biopsy samples have been reported"
"The GI microbiota plays an essential role in physiological homeostasis in the intestine and periphery, including maintaining resistance to infection, stimulating immunological development, and perhaps even influencing brain development and behavior. Thus, disruption of the balanced communication between the microbiota and the human host could have profound effects on human health."
"In our previous metagenomic study, we found sequences corresponding to members of the family Alcaligenaceae in the class Betaproteobacteria that were present in ileal and cecal biopsy samples from 46.7% (7/15) of AUT-GI children... Several members of Alcaligenaceae cause clinically relevant infections or are suspected opportunistic pathogens in humans and animals, including members of the genus Bordetella (including the human respiratory pathogens B. pertussis and B. parapertussis."
This is an earlier study done by the same researchers, the findings of which were the basis for the study referenced above. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances
"Reports of deficiencies in disaccharidase enzymatic activity and of
beneficial responses to probiotic and dietary therapies led us to survey
gene expression and the mucoepithelial microbiota in intestinal
biopsies from children with autism and gastrointestinal disease and
children with gastrointestinal disease alone. Ileal transcripts encoding
disaccharidases and hexose transporters were deficient in children with
autism, indicating impairment of the primary pathway for carbohydrate
digestion and transport in enterocytes. Deficient expression of these
enzymes and transporters was associated with expression of the
intestinal transcription factor, CDX2. Metagenomic analysis of
intestinal bacteria revealed compositional dysbiosis manifest as
decreases in Bacteroidetes, increases in the ratio of Firmicutes to
Bacteroidetes, and increases in Betaproteobacteria. Expression levels of
disaccharidases and transporters were associated with the abundance of
affected bacterial phylotypes. These results indicate a relationship
between human intestinal gene expression and bacterial community
structure and may provide insights into the pathophysiology of
gastrointestinal disturbances in children with autism."
More research about Suterella and intestinal health and function:
Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder
"We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder."
"A previous study by our group used quantitative real-time PCR (QPCR) to
compare the abundance of a range of bacteria in feces of children with
ASD, their siblings and community controls, and demonstrated a low
relative abundance of Bifidobacterium spp. and the mucolytic bacterium Akkermansia muciniphila in children with ASD" (Here is the study link:
Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism )
"Our results demonstrate that numbers of Sutterella are elevated in the feces of children with ASD relative to community controls. This confirms and builds on the findings of Williams et al."
"In this study we also extended our analysis of mucus-degrading bacteria
in feces of ASD children, having previously shown a low abundance of the
mucolytic bacterium A. muciniphila. We measured the abundances of R. torques and R. gnavus, both of which can degrade mucus and have been associated with GI disturbance. We have shown there is a trend of increased fecal numbers of R. torques in ASD children. This pattern of decreased numbers of A. muciniphila but increased numbers of R. torques in feces of ASD children is congruent with the pattern observed in the mucosa of adults with IBD. In the latter study it was also found that growth of A. muciniphila
was inhibited by co-culture with MUC2, the predominant form of mucin in
the large bowel, whereas this mucin augmented the growth of other
bacteria such as R. torques. Although it is likely that the
populations and activities of microbes that adhere to the mucus lining
the large bowel may differ substantially from those in the feces, it is
also likely that some changes in gut mucosal microbial populations are
reflected in, and hence detectable in, feces. Changes in the amount of
mucus produced may drive changes in mucus-degrading microbes in both the
mucosa and in feces, as mucus can be incorporated into the fecal
stream. Individuals with IBD or ASD may have changes in large bowel
mucus production that could impact (or are a result of changes in) the
mucosal barrier of the gut. Indeed, increased gut permeability has been
reported in a subgroup of children with ASD."
Metagenomics revealed a correlation of gut phageome withautism spectrum disorder
“The public microbiota database of ASD and typically developing (TD) Chinese
individuals were analyzed for phage protein-coding units (pPCU) to find any
link between the phageome and ASD. The gut phageome of ASD individuals showed a
wider diversity and higher abundance compared to TD individuals. The ASD
phageome was associated with a significant expansion of Caudoviricetes
bacteriophages. Phages infecting Bacteroidaceae and prophages encoded
within Faecalibacterium were more frequent in ASD than in TD
individuals. The expansion and diversification of ASD phageome can influence
the bacterial homeostasis by imposing pressure on the bacterial communities. In
conclusion, the differences of phages community in in ASD and TD can be used as
potential diagnosis biomarkers of ASD. Further investigations are needed to
verify the role of gut phage communities in the pathogenesis of ASD.”
