Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

Results: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phage deep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).

Conclusions: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

Human Papillomavirus, or HPV, is a viral pathogen that most commonly spreads through sexual contact. HPV strains 6 and 11 normally cause genital warts, while HPV strains 16 and 18 commonly cause cervical cancer, which causes cancerous cells to spread in the cervix. Physicians can detect those HPV strains, using a Pap smear, which is a diagnostic test that collects cells from the female cervix.

In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar stage of development. Had the flies not been manipulated, they would have developed into adults with vermilion eyes. (2) Beadle and Ephrussi transplanted the donor optic discs into the bodies of several types of larvae, including those that would develop with normal colored eyes (brick red), and those that would develop eyes with other shades of red, such as claret, carmine, peach, and ruby (grouped together and colored black in the image). (3a) When implanted into normal hosts that would develop brick red eyes, the transplanted optic disc developed into an eye that also was brick red. (3b) When implanted into abnormal hosts that would develop eyes of some other shade of red, the transplanted optic discs developed into eyes that were vermilion. Beadle and Ephrussi concluded that there was a factor, such as an enzyme or some other protein, produced outside of the optic disc that influenced the color of the eye that developed from the disc.

This illustration shows George Beadle and Edward Tatum's experiments with Neurospora crassa that indicated that single genes produce single enzymes. The pair conducted the experiments at Stanford University in Palo Alto, California. Enzymes are types of proteins that can catalyze reactions inside cells, reactions that produce a number of things, including nutrients that the cell needs. Neurospora crassa is a species of mold that grows on bread. In the early 1940s, Beadle and Tatum conducted an experiment to discover the abnormal genes in Neurospora mutants, which failed to produce specific nutrients needed to survive. (1) Beadle and Tatum used X-rays to cause mutations in the DNA of Neurospora, and then they grew the mutated Neurospora cells in glassware. (2) They grew several strains, represented in four groups of paired test tubes. For each group, Neurospora was grown in one of two types of growth media. One medium contained all the essential nutrients that the Neurospora needed to survive, which Beadle and Tatum called a complete medium. The second medium was a minimal medium and lacked nutrients that Neurospora needed to survive. If functioning normally and in the right conditions, however, Neurospora can produce these absent nutrients. (3) When Beadle and Tatum grew the mutated mold strains on both the complete and on the minimal media, all of the molds survived on the complete media, but not all of the molds survived on the minimal media (strain highlighted in yellow). (4) For the next step, the researchers added nutrients to the minimal media such that some glassware received an amino acid mixture (represented as colored squares) and other glassware received a vitamin mixture (represented as colored triangles) in an attempt to figure out which kind of nutrients the mutated molds needed. The researchers then took mold from the mutant mold strain that had survived on a complete medium and added that mold to the supplemented minimal media. They found that in some cases the mutated mold grew on media supplemented only with vitamins but not on media supplemented only with amino acids. (5) To discover which vitamins the mutant molds needed, Beadle and Tatum used several tubes with the minimal media, supplementing each one with a different vitamin, and then they attempted to grow the mutant mold in each tube. They found that different mutant strains of the mold grew only on media supplemented with different kinds of vitamins, for instance vitamin B6 for one strain, and vitamin B1 for another. In experiments not pictured, Beadle and Tatum found in step (4) that other strains of mutant mold grew on minimal media supplemented only with amino acids but not on minimal media supplemented only with vitamins. When they repeated step (5) on those strains and with specific kinds of amino acids in the different test tubes, they found that the some mutated mold strains grew on minimal media supplemented solely with one kind of amino acid, and others strains grew only on minimal media supplemented with other kinds of amino acids. For both the vitamins and amino acid cases, Beadle and Tatum concluded that the X-rays had mutated different genes in Neurospora, resulting in different mutant strains of Neurospora cells. In a cell of a given strain, the X-rays had changed the gene normally responsible for producing an enzyme that catalyzed a vitamin or an amino acid. As a result, the Neurospora cell could no longer produce that enzyme, and thus couldn't catalyze a specific nutrient.