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A digital twin of the infant microbiome to predict neurodevelopmental deficits.

ABSTRACT: Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R² = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (M_δ) and identify infants achieving poor future head circumference growth with ≈76% area under the receiver operator characteristic curve, 95% ± 1.8% positive predictive value at 98% specificity at 30 weeks postmenstrual age. We find that early transplantation might mitigate risk for ≈45.2% of the cohort, with potentially negative effects from incorrect supplementation. Q-nets are generative artificial intelligence models for ecosystem dynamics, with broad potential applications.

SUBMITTER: Sizemore N

PROVIDER: S-EPMC11006218 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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A digital twin of the infant microbiome to predict neurodevelopmental deficits.

Sizemore Nicholas N Oliphant Kaitlyn K Zheng Ruolin R Martin Camilia R CR Claud Erika C EC Chattopadhyay Ishanu I

Science advances 20240410 15

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16<i>S</i> ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts ab ...[more]

PMID: 38598636

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Project description:BackgroundTwin-to-twin transfusion syndrome (TTTS) is a serious complication of 10-15% of twin or triplet pregnancies in which multiple fetuses share a single placenta. Communicating placental vessels allow one fetus (the donor) to pump blood to the other (the recipient). Mortality rates without intervention are high, approaching 100% in some series, with fetal deaths usually due to cardiac failure. Surgical correction using laser photocoagulation of communicating placental vessels was developed in the 1980s and refined in the 1990s. Since it was introduced in Victoria in 2006, laser surgery has been performed in approximately 120 pregnancies. Survival of one or more fetuses following laser surgery is currently > 90%, however the neurodevelopmental outcomes for survivors remain incompletely understood. Prior to laser therapy, at least one in five survivors of TTTS had serious adverse neurodevelopmental outcomes (usually cerebral palsy). Current estimates of neurological impairment among survivors following laser surgery vary from 4 to 31% and long-term follow-up data are limited.MethodsThis paper describes the methodology for a retrospective cohort study in which children aged 24 months and over (corrected for prematurity), who were treated with laser placental photocoagulation for TTTS at Monash Health in Victoria, Australia, will undergo comprehensive neurodevelopmental assessment by a multidisciplinary team. Evaluation will include parental completion of pre-assessment questionnaires of social and behavioural development, a standardised medical assessment by a developmental paediatrician or paediatric neurologist, and age-appropriate cognitive and academic, speech and fine and gross motor assessments by psychologists, speech and occupational therapists or physiotherapists. Assessments will be undertaken at the Murdoch Children's Research Institute/Royal Children's Hospital, at Monash Health or at another mutually agreed location. Results will be recorded in a secure online database which will facilitate future related research.DiscussionThis will be the first study to report and evaluate neurodevelopmental outcomes following laser surgery for twin-to-twin transfusion syndrome in Victoria, and will inform clinical practice regarding follow-up of children at risk of adverse outcomes.

Project description:BackgroundNeurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear.MethodsHere, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores.ResultsWe found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile).LimitationsIn the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules.ConclusionsThese findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.

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A digital twin of the infant microbiome to predict neurodevelopmental deficits.

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A digital twin of the infant microbiome to predict neurodevelopmental deficits.

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