Antibiotics have been used for hundreds of years to treat infection. Indeed, some two thousand years ago Egyptians applied moldy bread to treat infected wounds. However, the active ingredient in moldy bread, useful in fighting infections, was not discovered until 1928 by Alexander Flemming. From then on, some 14 years elapsed before penicillin was mass produced. Commercially available penicillin was initially tested in a group of burn victims that had received skin grafts. The treatment proved miraculous, helping patients recover from what would have been a very painful death. Soon afterwards the military tested it for its troops (1943). In World War II the need for penicillin was so great that during those perilous years the army made use of 85% of the nation’s supply.
Besides treating bacterial infections antibiotics have had some unexpected benefits in health care. They are used in chemotherapy as they allow clinicians to be more aggressive inducing immunosuppression in cancer patients. They are also used routinely in transplants and as preventive treatment for surgical procedures. Unfortunately, not long after the introduction of antibiotics bacteria started building resistance against them. Being massively prescribed meant that in many occasions they were administered inadequately; using incorrect dosages and/or duration. Furthermore, with the use of antibiotics there has been an inverse relationship to prototypical infectious diseases and a direct relationship to immune disorders (e.g., diabetes and asthma). It should be stressed that this correlation between antibiotic use and immune disorders does not imply causation. Obesity, a confound leading to diabetes, has also increased during the time period of increased antibiotic use.
A recent article by Strati et al. published in Microbiome 2017 provides evidence of an altered microbiome in autism spectrum disorder (ASD). The finding is of importance as it may lead to potential new intervention strategies in the treatment of autism. (Note: Another recent article, of great interest, claims that alteration of the oral microbiota differentiates ASD children from controls. The results correlated with behavioral severity scores. This opens the possibility of using saliva tests as complementary diagnostic tests for ASD. See reference for Qiao et al., 2018)
Some helpful explanations may be needed at this point in time. The term microbiome makes reference to the aggregate of microorganisms that reside on the surface and deep layers of skin, oral mucosa, conjunctiva, and gastrointestinal track. Within the human body there are 10x as many microbial cells as human cells; including bacteria, fungi and viruses. This relationship has proven to be of mutual benefit. The host provides a stable environment, temperature and nutrients to his microbiota. In return, microbes provide us with vitamins and micronutrients such as retinol, riboflavin, folate, biotin, and niacin. The microbiota also reduces our sensitivity to certain pathogens and influences the metabolism of drugs (Swanson, 2015).
Another useful term to understand is metabolomics. The term makes reference to the characterization by mass spectroscopy or other analytical methods of metabolites generated by one or more organisms in a given physiological and environmental context. Metabolomics allows for a better understanding of the dynamic operations of microbial communities.
Going back to Strati’s (2017) article, there is little to incriminate the use of antibiotics in altering the microbiota of autistic individuals. Although anecdotal accounts describe an increase number of infections during childhood years, empirical studies tend to disprove this account (Rosen et al., 2007). In addition, studies on the microbiome in any population are quite difficult as the microbiota of the gut is highly variable among individuals and throughout their lifetimes. In this regard, a person’s microbiome is not fixed and when experiencing some disturbance the ensuing change varies among individuals. It may be that the microbiome in ASD individuals is different to that of control subjects; however, changes may be due to dietary factors, nutritional deficiency (e.g., iron, magnesium), and changes in bowel habits (see references below).
The use of antibiotics early in life in ASD needs to be further studied. Available studies are scarce and prevent us from drawing hard conclusions. The importance of performing further studies is highlighted by some observations of relevance to autism:
- Studies have shown that more patients with inflammatory Bowel Disease (IBD) may have had one or more antibiotics dispensations in their first year of life as compared to controls (58% vs 39% in one study). Those receiving one or more dispensation of antibiotics were 2.9 times the odds of being suffering from inflammatory bowel disease.
- There is a link between the microbiome and obesity. Diet and exercise don’t seem to be enough to control weigh in all individuals. A study published in Nature in 2006 by Turbaugh et al. took adult germ-free mice and colonized them with microbiota from either obese or lean mice. Over several weeks the ones that got the obese donor gained significant fat. Those that turned obese were also colonized by more firmicutes, a bacteria now associated with poor weigh control. This experiment has now been reproduced in human (Vrieze et al, 2012). The latter study showed how intestinal microbiota from lean donors when transplanted to males with metabolic syndrome showed improvements in peripheral insulin sensitivity without a difference in diet composition.
There are some additional aspects of autism that may relate to the microbiota (e.g., anxiety) but evidence for them being a factor in autism is peripheral. What we have as of present are intriguing correlations that suggest the need for further studies. In terms of immediate applications, we need targeted, rapid turn-around tests to describe our microbiota and we need to emphasize the use of narrow spectrum antibiotics in our clinical practice.
For those interested there is related information in some of our previous blogs:
Qiao Y, Wu M, Feng T, et al. Alterations of oral microbiota distinguish children with autism spectrum disorder from healthy control. Scientific Reports, article number 1597, 2018.
Rosen NJ, Yoshida CK, Croen LA. Infection in the first 2 years of life and autism spectrum disorders. Pediatrics 119(1):e61-69, 2007.
Strati F, Cavaleri D, Albanese D, et al. New evidence on the altered gut microbiota in autism spectrum disorders. Microbiome 5:24, 2017.
Swanson H. Drug metabolism by the host and gut microbiota: a partnership or rivalry? Drug Metabo Dispos 43(10): 1499-1504, 2015.
Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obeity-associated gut microbiome with increased capacity for energy harvesting. Nature 444:1027-1032, 2006.
Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroeneterology 143(4):913-916, 2012.