Biology subjects

Adams, J. B.

Publications and source records attributed to Adams, J. B..

5 recordsLinked to original sources

bioRxiv2025

Multi-omics Integration of Microbiota Transplant Therapy in Children with Autism Spectrum Disorders

BackgroundMicrobiota transplant therapy (MTT) is a promising avenue for the substantial improvement of gastrointestinal and behavioral symptoms in children with autism spectrum disorder (ASD). Previous work has demonstrated that microbiome and metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following MTT. MethodsTo enhance a systems-level understanding of MTT in ASD children that extends beyond previously reported findings, we present a multi-omics analysis of an ASD cohort spanning 10 weeks and 2 years of follow-up after completion of MTT. We applied cutting-edge multi-omics approaches, including metagenomics, fecal and plasma metabolomics, and advanced statistical methods, including multimodal machine learning, differential network analysis, and causal mediation analysis, to extensively characterize molecular and biochemical responses before and after MTT, to identify key taxonomic, functional, and metabolite signatures associated with MTT treatment and ASD symptoms. ResultsUsing a combination of cross-sectional and longitudinal statistical analyses and integrative machine learning techniques, we identified key meta-omic features associated with MTT. Integrated multi-omics analysis revealed that children with ASD transition to distinct biological states following MTT, clearly separated from their pre-treatment states and from TD children, as demonstrated by robust group separation and strong classification performance. Several biological signals associated with the modulation of the gut microbiome after MTT were identified, including an increase of butyrate producers such as Faecalibacterium prausnitzii and Butyricimonas faecalis; decreased fecal sulfated primary bile acid, chenodeoxycholic acid sulfate; decreased secondary bile acid, glycolithocholate sulfate; and increased sarcosine and iminodiacetate in plasma after 10 weeks of MTT compared to baseline. Differential network analysis revealed hub species, including Prevotella copri, Ruminococcus callidus, and GGB9633 SGB15091, as differentially connected 2 years after completion of MTT compared to baseline. Mediation analysis uncovered several key players as mediators of symptoms, including Alistipes ihumii, Ruminococceae, amino acid biosynthesis, bile acids, long-chain fatty acids, and cysteine-glutathione disulfide, among others. ConclusionsThis study provides one of the first comprehensive analyses of multi-omic features underlying host-microbiome interactions associated with MTT in children with ASD. It offers further evidence that fusing data across diverse molecular modalities at pre- and post- treatment time points can illuminate the potential of MTT in neurodevelopmental disorders. These findings could advance microbiome-based immunomodulatory therapies and multi-omics strategies to restore gut microbiota in children with ASD, while aiding in the discovery of novel biomarkers predictive of treatment response.

systems biology↗

bioRxiv2024

Reanalysis of metabolomics data reveals that microbiota transfer therapy modulates important fecal and plasma metabolite profiles in children with autism spectrum disorders

While Autism Spectrum Disorder (ASD) is diagnosed through behavioral symptoms and psychometric evaluations, it has also been associated with distinct metabolomic patterns. A previous clinical trial of Microbiota Transplant Therapy (MTT) in children with ASD and gastrointestinal (GI) issues revealed significant differences in plasma metabolomics between children with ASD and their typically developing (TD) counterparts, which diminished after MTT. The objective of this study was to reanalyze the plasma and fecal samples using updated metabolomics libraries at Metabolon together with a comprehensive panel of statistical methods to provide deeper insights into ASD-related metabolic differences and the impact of MTT. Compared with the original analysis, the updated annotation identified substantially more annotated metabolites and uncovered additional plasma and fecal metabolic changes associated with MTT. The reanalysis highlighted specific metabolites whose relative peak intensities differed between the ASD and TD groups, as well as metabolites with significant changes following MTT. Several plasma metabolites, including sarcosine, iminodiacetate, caproate, and caprylate, initially showed significant differences between the ASD and TD groups but shifted to resemble TD levels after MTT. In fecal samples, p-cresol sulfate and sphingolipids emerged as metabolites with altered intensities following MTT. Multivariate Fishers Discriminant Analysis (FDA) with leave-one-out cross-validation revealed that a set of metabolites including p-cresol sulfate, hydroxyproline, and caprylate could robustly classify the ASD and TD cohorts before treatment. However, after treatment, the same FDA model could no longer distinguish the two groups, as FDA scores became similar to those of the TD cohort. These findings improve our understanding of ASD-associated metabolic alterations and demonstrate that reanalysis of existing untargeted metabolomics datasets using updated metabolite annotation resources and complementary statistical approaches can reveal biologically relevant metabolite changes that were not detected previously. Larger studies with placebo-controlled designs are needed to validate these findings, further define the underlying biochemical pathways, and evaluate their potential for developing personalized therapeutic strategies. IMPORTANCEReanalysis of existing untargeted metabolomics datasets using updated metabolite annotation resources and complementary statistical approaches can reveal biological insights that were not apparent in earlier analyses. By leveraging updated metabolomics libraries and expanded statistical analyses, we identified additional annotated metabolites and uncovered plasma and fecal metabolic changes associated with autism spectrum disorder (ASD) and Microbiota Transplant Therapy (MTT). Several metabolites, including sarcosine, caprylate, and p-cresol sulfate, distinguished children with ASD from typically developing (TD) controls at baseline and shifted toward TD-like profiles following MTT. These findings demonstrate the value of periodically reanalyzing legacy metabolomics datasets as annotation resources improve, providing a more comprehensive understanding of disease-associated metabolic alterations and therapeutic responses.

neuroscience↗

bioRxiv2024

Soil carbon in the world's tidal marshes

Tidal marshes are threatened coastal ecosystems known for their capacity to store large amounts of carbon in their water-logged soils. Accurate quantification and mapping of global tidal marshes soil organic carbon (SOC) stocks is of considerable value to conservation efforts. Here, we used training data from 3,710 unique locations, landscape-level environmental drivers and a newly developed global tidal marsh extent map to produce the first global, spatially-explicit map of SOC storage in tidal marshes at 30 m resolution. We estimate the total global SOC stock to 1 m to be 1.44 Pg C, with a third of this value stored in the United States of America. On average, SOC in tidal marshes 0-30 and 30-100 cm soil layers are estimated at 83.1 Mg C ha-1 (average predicted error 44.8 Mg C ha-1) and 185.3 Mg C ha-1 (average predicted error 105.7 Mg C ha-1), respectively. Our spatially-explicit model is able to capture 59% of the variability in SOC density, with elevation being the strongest driver aside from soil depth. Our study reveals regions with high prediction uncertainty and therefore highlights the need for more targeted sampling to fully capture SOC spatial variability.

ecology↗

bioRxiv2023

Bimodal distribution of Candida albicans in children with Autism linked with ASD symptoms

The gastrointestinal (GI) tract harbors an intricate and remarkably diverse microbial ecosystem that profoundly impacts various aspects of health and pathophysiology. While bacteria overwhelmingly represent most of the GI microbiota, it is imperative to consider the presence and function of fungal constituents (i.e., mycobiota) within the GI ecosystem. The substantial incidence of GI disorders and associated manifestations in children diagnosed with autism spectrum disorder (ASD) suggests a plausible contributory role of the gut mycobiota. Our investigation aimed to elucidate the gut mycobiota in a cohort comprising 38 typically developing children (TD) and 40 children with ASD. Fecal samples were collected from all participants and autism severity and GI symptoms were assessed to unravel the potential implications of mycobiota alterations in the gut. We employed fungal internal transcribed spacer (ITS) gene amplicon sequencing to analyze the fungal composition and investigate their relationship with GI and autism symptoms. Among gut mycobiota, Saccharomyces cerevisiae was significantly lower (relative abundance) in ASD compared to TD children. Total Candida and C. albicans demonstrated a bimodal distribution among children with ASD. Children with ASD with elevated Autism Treatment Evaluation Checklist (ATEC) scores (a more severe diagnosis) displayed an increased abundance of C. albicans and a decreased abundance of S. cerevisiae. A significant positive correlation was observed between ATEC scores and GI symptoms and between ATEC scores and C. albicans. Our findings propose that a deficit of beneficial fungi, specifically S. cerevisiae, and an overgrowth of C. albicans may worsen autism severity in children with ASD. Future work employing more advanced techniques (i.e., shotgun metagenomics) is encouraged to advance understanding of the functional role of fungi/yeast, and their interplay between GI symptoms and autism severity in children with ASD.

microbiology↗

bioRxiv2023

Interactive effects of salinity, temperature and food web configuration on performance and harmfulness of the raphidophyte Heterosigma akashiwo

The cosmopolitan raphidophyte Heterosigma akashiwo commonly forms harmful algal blooms (HABs) in diverse estuaries discharging into Algoa Bay, South Africa, potentially leading to hypoxia, fish kills and a decline in key primary consumers. Despite the high environmental variability in these estuaries, little is known about how abiotic factors such as temperature and salinity constrain bloom formation and harmfulness of H. akashiwo. The present study therefore investigates growth, competition, and grazing interactions of H. akashiwo in laboratory experiments in response to two naturally relevant levels of salinity (15, 30) and temperature (16, 22{degrees}C), respectively. Experiments were set up with the naturally co-occurring dinoflagellate competitor Heterocapsa rotundata and two estuarine microzooplankton consumers, i.e., nauplii of the copepod Acartia tonsa and the rotifer Brachionus plicatilis. In monoculture, H. akashiwo growth was promoted at high temperature - low salinity conditions, while H. rotundata thrived under low temperature - high salinity conditions. In polyculture, H. akashiwo dominated at high temperature irrespective of the salinity regime, while at low temperature, it only dominated at low salinity and was suppressed by H. rotundata at high salinity. Grazing assays revealed highly negative effects of H. akashiwo on copepod nauplii survival and growth as well as mucus-induced immobilization, especially at high temperatures in combination with low salinity, while the estuarine adapted rotifers showed highest mortalities at the higher salinity level. The presence of H. rotundata significantly alleviated the harmful effects of H. akashiwo on both grazers, and the selectively feeding copepod nauplii actively avoided H. akashiwo when non-harmful prey was present. Overall, this study demonstrates that population dynamics and harmful effects of H. akashiwo are interactively determined by both abiotic conditions and food web configuration, implying competitor and consumer specific tolerances to the abiotic environment and their susceptibility to the harmful alga H. akashiwo.

ecology↗