Urinary organic acids spectra in children with altered gut microbiota composition and autistic spectrum disorder

Daneberga, Zanda; Nakazawa-Miklaševiča, Miki; Berga-Švītiņa, Egija; Murmane, Daiga; Isarova, Dana; Cupane, Liene; Masinska, Madara; Nartisa, Inga; Lazdane, Andzela; Miklaševičs, Edvīns

doi:10.1080/08039488.2021.2014954

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Overall, the selected studies included a total of 2.079 individuals diagnosed with ASD (1.625 males, 394 females; mean age of 10,9 years), 51 individuals with other psychiatric comorbidities (developmental delays), 182 at-risk individuals (siblings, those with genetic conditions) and 1.530 healthy controls (TD). Sixteen of these studies were carried out in Europe [21,22,24,25,[29][30][31]35,37,39,41,44,45,47,52,56], twelve in Asia [23,28,33,34,36,40,42,43,46,50,54,55,58], eight in the USA [27,32,38,48,49,51,53,57] and one in Australia [58].…”

Section: Discussionmentioning

confidence: 99%

“…Noteworthy, other authors highlight the need to employ with caution metabolomic results (the perturbated concentration of fecal or urinary gut-derived metabolites) as indirect indicators of gut dysbiosis (microflora species richness and diversity)-and subsequently as biomarkers as GI disorders-suggesting a combined use of microbiota analysis and metabolomics [56].…”

Section: Gastrointestinal Disordersmentioning

confidence: 99%

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Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder

Siracusano,

Arturi,

Riccioni

et al. 2023

IJMS

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Precision medicine is imminent, and metabolomics is one of the main actors on stage. We summarize and discuss the current literature on the clinical application of metabolomic techniques as a possible tool to improve early diagnosis of autism spectrum disorder (ASD), to define clinical phenotypes and to identify co-occurring medical conditions. A review of the current literature was carried out after PubMed, Medline and Google Scholar were consulted. A total of 37 articles published in the period 2010–2022 was included. Selected studies involve as a whole 2079 individuals diagnosed with ASD (1625 males, 394 females; mean age of 10, 9 years), 51 with other psychiatric comorbidities (developmental delays), 182 at-risk individuals (siblings, those with genetic conditions) and 1530 healthy controls (TD). Metabolomics, reflecting the interplay between genetics and environment, represents an innovative and promising technique to approach ASD. The metabotype may mirror the clinical heterogeneity of an autistic condition; several metabolites can be expressions of dysregulated metabolic pathways thus liable of leading to clinical profiles. However, the employment of metabolomic analyses in clinical practice is far from being introduced, which means there is a need for further studies for the full transition of metabolomics from clinical research to clinical diagnostic routine.

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Section: Discussionmentioning

confidence: 99%

Section: Gastrointestinal Disordersmentioning

confidence: 99%

Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder

Siracusano,

Arturi,

Riccioni

et al. 2023

IJMS

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“…It is reported that various species within the Firmicutes family of Clostridiaceae are involved in p -cresol production from tyrosine and phenylalanine via fermentation [ 71 , 72 , 73 , 74 ]. Elevated levels of Clostridiaceae species in fecal samples from ASD patients have been reported [ 75 , 76 ], and several studies have shown that p -cresol metabolites , p CS or p CG, are elevated in urine and feces of autistic children associated with altered gut microbiota composition [ 34 , 35 , 77 ]. P -cresol alters dopamine metabolism, enhances glutamine, and decreases γ-aminobutyric acid in autistic children [ 12 , 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

The Autism Spectrum Disorder-Associated Bacterial Metabolite p-Cresol Derails the Neuroimmune Response of Microglial Cells Partially via Reduction of ADAM17 and ADAM10

Zheng

Prince

Marzal

et al. 2022

IJMS

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The bacterial metabolite 4-methylphenol (para-cresol or p-cresol) and its derivative p-cresyl sulfate (pCS) are elevated in the urine and feces of children with autism spectrum disorder (ASD). It has been shown that p-cresol administration induces social behavior deficits and repetitive behavior in mice. However, the mechanisms of p-cresol, specifically its metabolite pCS that can reach the brain, in ASD remain to be investigated. The pCS has been shown to inhibit LPS-stimulated inflammatory response. A Disintegrin And Metalloprotease 10 (ADAM10) and A Disintegrin And Metalloprotease 17 (ADAM17) are thought to regulate microglial immune response by cleaving membrane-bound proteins. In the present study, a neuroinflammation model of LPS-activated BV2 microglia has been used to unveil the potential molecular mechanism of pCS in ASD pathogenesis. In microglial cells pCS treatment decreases the expression or maturation of ADAM10 and ADAM17. In addition, pCS treatment attenuates TNF-α and IL-6 releases as well as phagocytosis activity of microglia. In in vitro ADAM10/17 inhibition experiments, either ADAM10 or ADAM17 inhibition reduces constitutive and LPS-activated release of TNF-α, TNFR-1 and IL-6R by microglial cells, while it increases constitutive and LPS-activated microglial phagocytotic activity. The in vivo results further confirm the involvement of ADAM10 and ADAM17 in ASD pathogenesis. In in utero VPA-exposed male mice, elevated concentration in serum of p-cresol-associated metabolites pCS and p-cresyl glucuronide (pCG) is associated with a VPA-induced increased ADAM10 maturation, and a decreased ADAM17 maturation that is related with attenuated levels of soluble TNF-α and TGF-β1 in the mice brain. Overall, the present study demonstrates a partial role of ADAM10 and ADAM17 in the derailed innate immune response of microglial cells associated with pCS-induced ASD pathogenesis.

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“…Therefore, each population could also show the typical pattern of gut microbiota. Up to now, only a few studies have been published about gut microbiota composition in Latvian children, and no data exist about early-life microbiota (Kroièa et al, 2020;Daneberga et al, 2021). The aim of the present study was to analyse the composition of gut microbiota and influencing factors in infants up to seven months of age in Latvia, in respect of the type of delivery, nutrition, and some other environmental factors.…”

Section: Introductionmentioning

confidence: 98%

Dominating taxonomic composition of the early life gut microbiota and influencing factors in infants up to seven months of age in Latvia

Zelča

Gudrā

Lūse

et al. 2022

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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It has been hypothesised that the establishment of stable adult microbiota is programmed in infancy, and therefore early life gut colonisation may lead to a lifelong microbiota pattern with significant effects on health. The aim of the study was to analyse the composition of gut microbiota and influencing factors in infants up to seven months of age in Latvia. A cross-sectional study was performed at primary healthcare centres. The parents of healthy infants filled out a questionnaire and brought the child’s faecal sample. 16 rRNS gene sequencing was performed to identify the bacterial taxonomic units. The composition of gut microbiota was compared between children with different risk factors. The final participant sample group included 55 infants with median age 4.0 months. The infant gut microbiota of the sample group had typical and rather healthy microbiota — the main phyla detected were Firmicutes and Actinobacteria, the main family was Bifidobacteriacea and genus — Bifidobacterium. A significant effect of the type of delivery and feeding type was identified, as well as negative correlation between Lactobacilli and gestational age. Further, it would be important to analyse the changes of microbiota prospectively to identify the association with environmental factors and health status in dynamics.

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Urinary organic acids spectra in children with altered gut microbiota composition and autistic spectrum disorder

Cited by 10 publications

References 24 publications

Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder

Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder

The Autism Spectrum Disorder-Associated Bacterial Metabolite p-Cresol Derails the Neuroimmune Response of Microglial Cells Partially via Reduction of ADAM17 and ADAM10

Dominating taxonomic composition of the early life gut microbiota and influencing factors in infants up to seven months of age in Latvia

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