Periodontopathic bacteria produce high concentrations of short-chain fatty acids (SCFAs) in their culture supernatant. Periodontopathic bacteria-produced butyric acid is an extracelluar metabolite that induces apoptosis in neutrophiles, T-cells and macrophages, and it has immunomodulatory properties and facilitates microbial transition in dental plaque. AIDS progression is associated with the development of severe periodontitis. One of our main objectives was to examine whether periodontopathic-bacteria infection facilitates viral progression by reactivating latent viral infections, such as HIV-1 and EBV. With regard to HIV-1, hyperacetylation of histone proteins by histone deacetylase (HDACs) is involved in maintenance of HIV-1 latency repressing HIV-1 proviral DNA-tanscription. We demonstrated that P. gingivalis-culture supernatant, containing butyric acid, acts as potent HDAC inhibitor, appearing to induce histone acetylation which eventually leads to HIV reactivation in latently infected cells. With regard to EBV, the EBV BZLF1 gene product, ZEBRA, is a master regulator in the transition from latency to the lytic replication cycle in latently infected B cells. We also demonstrated that P. gingivalis-culture supernatant inhibited HDACs, thus, increasing histone acetylation and BZLF1 transcriptional activity. Overall, our results suggest that periodontal disease may act as a risk factor in viral infectious disease reactivation in latently infected individuals. Moreover, these findings suggest that butyric acid-producing intestinal bacteria may be involved in the aggravation of viral infections. More importantly, these findings indicate the importance of studying metabolic by-products, such as SCFAs, that may affect microbial interactions, to help elucidate endogenous infection mechanisms.

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Autism is a spectrum of developmental disorders, with onset in early childhood, affecting social, communicative, and imaginative development. The dramatic increase in the incidence of autism in recent years has created an increased need to find effective treatments. A gut-brain linkage for autism has been proposed, based on gastrointestinal disorders commonly found in autistic subjects. This paper summarizes recent studies on the fecal flora of regressive autism subjects. In 1998, Bolte E., who is the mother of an autistic child, proposed a hypothesis. She had been felt that certain antimicrobial drugs may be a key factor in the adverse modification of the intestinal bacterial flora, adversely, preferentially favoring the potentially harmful bacteria that are normally suppressed by an intact normal intestinal microbiota. In particular, she nominated the neurotoxin producing Clostridium tetani as a candidate autism-associated bacterium. To establish this hypothesis, Finegold S. M. and his research group carried out a series of studies on the fecal flora of autism subjects by using good use of both culture dependent and independent methods. They initially proposed that anaerobic spore-formers (Order Clostridiales including C. tetani and Clostridium bolteae) might be involved in regressive autism. More recently they have proposed Desulfovibrio, which is resistant to several antibiotics often used in childhood, as a novel autism-associated bacteria. Desulfovibrio have a special characteristics which account for much of the pathophysiology seen in autism. More recently, from another viewpoint, Williams B. L. and his research group have reported the association of high levels of mucosa-associated Sutterella species in the gut and gastrointestinal disturbances in autistic subjects. Studies of the fecal and mucosal microbiota of autistic subjects over the last two decades have opened a novel field in the etiology of autism.

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