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PEDIATRICS: PANS/ PANDAS SYNDROME ASSOCIATED WITH AN ALTERATION OF GUT MICROBIOTA

Distinct changes of the intestinal microbiota in subjects affected by PANS/PANDAS syndrome have been reported by Quagliariello et al. 2018 in a paper published by Frontiers in Microbiology.

This original study was carried out at the Bambino Gesù Children Hospital in collaboration with the Agostino Gemelli University Polyclinic and La Sapienza University of Rome. It is known that trillions of bacteria in the gut - the so-called microbiota - act as a biochemical plant for the whole organism. This "reactor" transforms the molecules derived from nutrients, to produce energy and regulates the intestinal mucosa immunity and the balance of microbial populations acting as a barrier against pathogens.

Therefore, the biochemical activities of the microbiota strongly influence all the body’s districts. Some studies have shown that the microbiota influences not only the intestinal but also the extra- intestinal homeostasis, acting on the behaviour and activities of the brain along the brain-intestine axis. In fact, several evidences indicate that intestinal microbiota affects the equilibrium of neuropathological behaviours, including stress, autism spectrum disorders, depression, multiple sclerosis, through immune, endocrine and neural signals.

It seems that microbiota interact with the brain via spinal cord, enteric nervous system, hypothalamic-pituitary- adrenal axis and central nervous system. This interaction is supported by the effects of probiotics and antibiotics on brain activity and functions. The brain-intestine axis is bidirectional. Microbial communities are regulated by environment, life-styles and individual characteristics. Since changes in the composition of the microbiota are associated with cognitive and behavioural alterations, a "healthy" or eubiotic microbiota is a prerequisite for the optimal regulation of intestinal-brain axis.

Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and the Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) are debated rare disorders, characterized by sudden and - at times - dramatic onset of neuropsychiatric symptoms (obsessions, compulsions, tics, food restrictions). The study published by Frontiers in Microbiology, a journal of the Nature group, analyzed and described the changes of the intestinal microbiota in PANS/PANDAS individuals. . In particular, in patients of 4-8 years of age, in which the microbiota’s profile has not been modified yet by antibiotic treatments currently used in these disorders, the microbiota profile was quite homogeneous, with a characteristic increase of some microbes, such as Bacteroides, Odoribacter and Oscillospira.

The metabolites involved in the modulation of the antibody and inflammatory response were increased in these patients, while those associated with the biochemical pathways involved in the brain function were decreased, in particular D-alanine, short-chain fatty acids, and the intermediates of tyrosine and dopamine. The research has been led by Dr. Lorenza Putignani, Parasitology and Human Microbiome Units of Bambino Gesù Children’s Hospital, prof. Francesco Cardona, Child and Adolescent Neuropsychiatry, La Sapienza, and prof. Antonio Gasbarrini, Gastroenterology and Medical Oncology of Gemelli.

The study suggested that streptococcal infections can alter intestinal bacterial communities, producing pro-inflammatory changes, through the selection of some distinct bacterial strains associated with intestinal inflammation and activation of the immune response, with a secondary reduced production of metabolites affecting brain activities, such as short-chain fatty acids, the precursors of D-alanine, tyrosine and the biochemical pathway of dopamine.

The study on PANS/PANDAS subjects, has not identified diagnostic biological markers, but has shown that the composition of intestinal microbiota can influence the behaviour, in agreement with other studies on patients with autism spectrum disorders. Present results stimulate a speculative debate on new potential therapeutic approaches in these patients.

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