Fecal Microbiota Transplantation (Autologous) in Infants Treated With Antibiotics

Antibiotics are lifesaving therapeutic drugs which have been used by adults, children, and infants alike for decades. There is an increase in global use of antibiotics over the course of lifetime and earlier in lifetime, with some countries recording as high as 12 courses a year in children younger than two. While antibiotics are successful in eradicating many pathogenic bacteria, research has demonstrated significant effect on beneficial gut microbiota, including long-lasting shift in the dynamics, composition, richness, and maturity of the intestinal flora.

Microbiota alterations during early life, including through antibiotics use as well as birth via C-section, constitute a developmental perturbation, which increases the risk of modern diseases of immune and metabolic dysfunction. Strong epidemiological evidence suggests associations between early stressors of the microbiota and a number of common diseases, such as obesity, asthma, allergies, celiac disease, and Type 1 Diabetes. There is evidence from mouse experiments of early perturbations in microbiota transmission at birth (such as C-section birthing) causing changes in the microbiome, increasing weight gain, and inhibiting intestinal expression of immune genes in neonates. Furthermore, excess antibiotic exposure is associated with the development of neurological and psychiatric disorders. Given the tendency of early perturbations to increase disease risks, it is important to evaluate effects of significant perturbations to microbiome at early ages, such as through antibiotic use.

Currently, no strategies exist to restore the microbiome other than reliance on spontaneous repair mechanism, which often takes months in a healthy individual barring further antibiotic exposure. Modern lifestyle and urban environments, however, work against this spontaneous repair, significantly reducing the microbiome diversity not only generationally but within an individual's lifespan. Contrary to popular belief, ingestion of probiotics, particularly after antibiotics, has been demonstrated to slow down the repair as it introduces an exogenous and massive amounts of only a few types of bacterial strains into a finely-tuned ecosystem of hundreds of different strains.

It is hypothesized that by preserving the child's microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant (FMT) will assist in a quick, effective, and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics. This would in turn reduce the overall loss of microbiome diversity over the child's lifespan, essentially providing a 'reset' option to the child's most unadulterated version of microbiome.

FMTs have been utilized, including in pediatric populations, to successfully treat recurring Clostridium difficile infections and are being investigated further as an adjunctive treatment in the management of ulcerative colitis, Crohn's Disease, and autism symptoms. Administration of heterologous FMTs (where recipient is different from donor), however, carry their own complexities - stool samples supplied by donors have to be identified and screened and are traditionally delivered in a medical setting as an out-patient procedure. The heterologous FMTs performed today layer the process with additional steps of ideal donor identification and sample screening for possible transmissible pathogens. This proposal uses an autologous sample, which means the sample comes from the healthy child and is administered to the same child after infection and the antibiotic course, conserving the absolutely unique diversity and heritage that that particular child's microbiome had before perturbation due to disease and antibiotics.