The Microbiome in Pediatric Rheumatic Diseases

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The human intestinal microbiota is home to more than 1,000 bacterial species, containing approximately 3 million genes, many of which code for functions that have the potential to affect human physiology.¹ Smaller numbers of organisms are also present in the skin, upper gastrointestinal tract, female reproductive tract and the oro- and nasopharynx. As tools have been developed in the past 10–15 years to query the microbiota, an enormous body of literature addressing the impact of the microbiota on a variety of chronic illnesses has emerged.

One particular condition that has been the subject of recent studies is juvenile idiopathic arthritis (JIA). Our group at the University of Alabama at Birmingham was the first to look at the microbiome in JIA, focusing exclusively on pediatric subjects with enthesitis-related arthritis (ERA, the pediatric version of spondyloarthritis), a condition with known genetic and clinical links to inflammatory bowel disease (IBD).²

We reported decreased fecal abundance of Faecalibacterium prausnitzii, a species with potential anti-inflammatory properties that also appears to be deficient in IBD patients.^3,4 Additionally, a subset of patients was identified with a markedly increased abundance of the Bacteroides genus.

The same genus was also shown to be elevated in a Finnish study of children with JIA, mostly with oligo-articular and poly-articular presentations; however, that study did not identify differences in the abundance of F. prausnitzii.⁵

These studies raise the possibility that some bacteria serve to promote arthritis in children, or even subsets of children, and others play a protective role.

Are There Good & Bad Microbiota?

These studies raise the possibility that there are some beneficial and some not-so-beneficial organisms. This is not a new hypothesis. The concept behind the hygiene hypothesis holds that alterations in the microbiota associated with modernization have resulted in an increased incidence of a variety of immune diseases, such as atopy and IBD.⁶

Although few would be nostalgic for high perinatal and childhood mortality, the notion that pre-industrialization microbiota may have something to offer us has gained traction. Along those lines, De Filippo et al compared the intestinal microbiota of young children, aged 2–6, in Florence, Italy, with those in a rural village in Burkina Faso, West Africa, a region characterized by an agrarian lifestyle and carbohydrate- and fiber-rich diets.⁷ There, they found substantial alterations in the intestinal micro­biota (see Table 1), including a striking expansion of the Prevotella genus in the Burkina Faso children, with this genus constituting over 50% of the microbiota, while being virtually undetectable in the Florence children. Additional differences included decreases in some potential pathogenic genera and increased microbial diversity observed in the Burkino Faso population. The authors argued that the totality of these findings indicated that the Burkina Faso children likely had a microbiota that could protect them against pathogens, as well as against inflammatory gastrointestinal diseases. It is, however, important to note that there are many differences aside from diet in these two highly diverse populations of children.