A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial

Abstract

Background: Recent experimental evidence suggests that gut microbiota may alter function within the nervous system providing new insight on the mechanism of neuropsychiatric disorders. Methods: Seventy-five infants who were randomized to receive Lactobacillus rhamnosus GG (ATCC 53103) or placebo during the first 6 mo of life were followed-up for 13 y. Gut microbiota was assessed at the age of 3 wk, 3, 6, 12, 18, 24 mo, and 13 y using fluorescein in situ hybridization (FISH) and qPCR, and indirectly by determining the blood group secretor type at the age of 13 y. The diagnoses of attention deficit hyperactivity disorder (ADHD) and Asperger syndrome (AS) by a child neurologist or psychiatrist were based on ICD-10 diagnostic criteria. results: At the age of 13 y, ADHD or AS was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (P = 0.008). The mean (SD) numbers of Bifidobacterium species bacteria in feces during the first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in healthy children 9.12 (0.64) log cells/g; P = 0.03. conclusion: Probiotic supplementation early in life may reduce the risk of neuropsychiatric disorder development later in childhood possible by mechanisms not limited to gut microbiota composition.P sychiatric disorders are already ranked among the leading causes of disability in industrialized countries. With the current progressive increase in the incidence, they may be expected to assume the first place also globally within the next few years (1,2). Attention-deficit hyperactivity disorder (ADHD), characterized by inattention, impulsivity, and hyperactivity, affects three to seven percent of children worldwide (3,4). Moreover, symptoms of inattention and hyperactivity are frequent in children with Asperger syndrome (AS), which is characterized by stereotyped behavior and deficient social interaction and communication skills (5). Besides the common behavioral features, shared biological pathways and neuroanatomical links between these diseases have been reported (5,6).Despite intensive research on ADHD and AS, the precise chain of pathological events underlying them remains unknown. The available data indicate ADHD and AS to be multifactorial disorders, in which genetic risk predominates, reinforced by various environmental and biological factors such as fetal stress, prematurity, toxins, and diet (7). Recently, the search for etiologies has been expanded both within the central nervous system and beyond. Experimental data are accumulating to suggest that the presence of gut microbiota as such, as compared with the absence of it, and especially its certain beneficial bacteria, probiotics, make for altered function within the nervous system (8-12). As a recent empirical study indicates (13) probiotics may provide a tool to manipulate brain activity even in humans.To test the hypothetical involvement of the gut brain-axis in the manifestation of ADHD and AS, we analyzed the association of compositional development of the gut microbiota, the...

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

“…The effect of the synbiotic intervention in the study cohort is only minor and does not explain the elevated levels, as similar effect was detected in both intervention groups-even during the intervention the bifidobacteria levels were not different between the groups. The observed elevated bifidobacterial levels in early life are potentially beneficial as previous reports suggest a protective role of bifidobacteria against excessive weight gain and neuropsychiatric disorders in later life (Kalliomäki et al, 2008;Pärtty et al, 2015).…”

Gut microbiome in health and disease: Linking the microbiome–gut–brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases

“…In one study, infants were given either Lactobacillus rhamnosus GG or placebo during the first 6 months of life and gut microbiota was assessed over a period of 13 years. The study found a correlation between lower counts of Bifidobacterium species and development of ADHD or Asperger’s Syndrome (Partty, Kalliomaki, Wacklin, Salminen, & Isolauri, 2015). …”

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…Social deficits in mice (less interest in social interaction, poor memory for social partners) [110,113] Reversal of social deficits in murine models of ASD [111,115] Reversal of antibiotic-induced social deficits in mice [113] Reduced risk for ASD [116] , reduced symptom severity in children with ASD (open pilot) [117] Transplant of standardized human gut microbiota to children with ASD improved ASD symptoms in open-label pilot [118] Pain Visceral hypersensitivity in mice [119] Visceral hypersensitivity in healthy mice [94,120,135] Reversal of visceral hypersensitivity in stressed mice [122] Increased risk for IBS in humans [51] Positive effects on pain in IBS patients [127] Reversal of stressinduced visceral hypersensitivity in rats [121] Reversal of antibiotic-induced visceral hypersensitivity in mice [135] Positive effects on IBS symptoms in humans [127] Transplant from IBS donors increases GI symptoms (accelerated gastrointestinal transit, increased intestinal permeability) in mice [125,126] Transplant from healthy donors reduces GI symptoms (constipation, diarrhea, indigestion, abdominal pain) in children with ASD (open-label pilot) [118] www.advancedsciencenews.com www.bioessays-journal.com been several studies reporting no effect of probiotics on these measures, [99] these disparate results may be explained by straindependent effects or a moderating effect of symptom severity because it has been reported that the beneficial effects are greatest for those with the most negative symptoms at baseline. [100] …”

“…Individuals with ASD often exhibit gastrointestinal problems and alterations in the microbiota. [115] Accordingly, preliminary pilot studies show that probiotics may reduce risk for ASD onset if administered perinatally [116] and reduce symptom severity in children already diagnosed with ASD. [117] In addition, significant improvements in gastrointestinal and behavioral symptoms were observed in an open pilot of faecal microbiota transplants for children with ASD.…”