The study, meticulously detailed in the journal Nature Communications, draws on longitudinal data from the comprehensive Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. By integrating microbiome profiles from stool samples collected at age two, functional brain connectivity imaging via resting-state MRI at age six, and behavioral assessments reported by caregivers at approximately seven-and-a-half years, the research team established a temporal framework for exploring how early microbial colonization patterns relate to subsequent emotional symptoms. This method enabled the identification of specific bacterial taxa—particularly those belonging to the Clostridiales order and Lachnospiraceae family—that were significantly enriched in children who later exhibited higher internalizing symptomatology.

What stands out in this work is the indirect mechanism proposed: rather than a straightforward correlation between gut bacteria and mental health symptoms, the gut microbiome appears to influence the functional architecture of emotion-related brain networks. The study highlights altered connectivity patterns within neural systems responsible for emotional regulation, positing that microbial constituents may modulate neurodevelopmental pathways that govern anxiety and depressive states. This neurobiological mediation underscores a sophisticated psychobiological dialogue between the microbiome and the brain, facilitated through pathways such as immunological signaling, vagal nerve communication, and microbial metabolite production.

Dr. Bridget Callaghan, the principal investigator and associate professor in UCLA’s Department of Psychology, emphasized the novelty and significance of the study in bridging gaps in current microbiome research. Prior investigations predominantly focused on infants and toddlers, whereas this study presents critical data about how early-life gut microbial composition reverberates into the functional organization of the brain by school age—a developmental period when internalizing symptoms first manifest in many children. By establishing a connection across this critical window, the research injects fresh momentum into understanding mental health etiologies and their microbial underpinnings.

Notably, the bacterial groups implicated—Clostridiales and Lachnospiraceae—are well-documented in adult literature to play roles in stress responsiveness and mood disorders. Their enrichment in young children predisposed to anxiety and depression evokes the possibility that the microbiome could serve as both a biomarker and a modifiable factor in the prevention and management of early-onset internalizing disorders. Given that these groups are also sensitive to early life adversities, the findings point towards a multifactorial model where environmental exposures, microbiota composition, and neural network development converge to shape mental health trajectories.

The analytical strategy deployed in the study mixed rigorous neuroimaging connectomics with advanced statistical modeling to parse out brain network signatures most predictive of internalizing symptoms. This synergy between microbiology and brain imaging is emblematic of interdisciplinary research aiming to decode the gut-brain axis. It presents a methodological blueprint for future investigations seeking to unravel causality in the microbiome-mental health nexus. The researchers identified specific connectivity alterations that correlated with the presence of certain gut microbes, demonstrating a nuanced biological embedding of the microbiota within neural circuitry relevant to emotion.

Despite the breakthroughs, the study authors caution that the evidence remains correlational, necessitating further experimental studies to establish causality. Pinpointing which species within the broad microbial groups are the true effectors remains a top priority. This granularity is essential to devise targeted interventions, such as precision probiotics or dietary modifications, which could recalibrate the microbiome towards neuroprotective profiles conducive to emotional resilience in children.

Co-first authors Drs. Francesca Querdasi and Jessica Uy contributed substantially to these findings, along with contributing insights from Dr. Jennifer S. Labus of UCLA Health. The collaborative effort spanned institutions across Singapore and included partners from A*STAR’s Institute for Human Development and Potential, KK Women’s and Children’s Hospital, the National University Health System, and the National University of Singapore Yong Loo Lin School of Medicine. This international research synergy underscores the global relevance and interdisciplinary nature of microbiome-mental health studies.

The broader thematic resonance of this study ties into an escalating scientific narrative that the trillions of microbes residing within our bodies—especially during critical developmental stages—are not mere bystanders but active architects of health and disease. The discovery of microbial influence on emotional brain networks represents a paradigm shift, inviting clinicians, neuroscientists, and microbiologists alike to consider holistic models of child development where microbial ecology is integral to mental health outcomes.

As the field advances, the prospect of leveraging microbiome modification as an adjunct or even preventative strategy for pediatric depression and anxiety offers exciting new horizons. By focusing on early life—a period of heightened neuroplasticity and microbial colonization—the research sets the stage for interventions that could attenuate or delay the onset of debilitating internalizing disorders, potentially reducing the substantial societal burden these conditions impose across the lifespan.

In conclusion, this UCLA Health study enriches our understanding of how the gut microbiome shapes the developing brain’s emotional circuitry and prefigures mental health in later childhood. It heralds a future where integrating microbiome science with developmental neurobiology could yield transformative strategies to promote psychological well-being from infancy through adolescence. This pioneering work propels the dialogue on mental health towards a microbiological dimension, offering hope for innovative, biologically informed interventions that align with the complex nature of emotional disorders.

Subject of Research: People
Article Title: Childhood gut microbiome is linked to internalizing symptoms at school age via the functional connectome
News Publication Date: 30-Oct-2025
Web References: https://www.nature.com/articles/s41467-025-64988-6
References: UCLA Health study published in Nature Communications, DOI: 10.1038/s41467-025-64988-6
Keywords: Gut microbiota, Psychiatric disorders, Depression, Anxiety, Age groups, Adolescents, Children

Cancer cells notoriously adapt their metabolism to meet the high energy and biosynthesis demands of uncontrolled growth. One hallmark of this adaptation is the preferential use of glycolysis, a quick but inefficient sugar breakdown pathway that generates metabolic intermediates essential for cell division. The UCLA team’s research uniquely identifies IGF2BP3 as a key modulator that not only modulates RNA but drastically shifts leukemia cells toward this glycolytic metabolism, highlighting a dual role that redefines conventional views of cellular regulation in cancer biology.

Professor Dinesh Rao, leading the study at UCLA’s David Geffen School of Medicine, emphasizes the surprising breadth of IGF2BP3’s influence, stating that its contribution to metabolic remodeling was unexpected and highly significant. This novel insight uncovers an intricate interplay between gene expression control at the RNA level and energy metabolism, processes long assumed to operate separately in cancer cells. The discovery implies that impeding IGF2BP3 could simultaneously halt the metabolic fueling and protein synthesis machinery that leukemia cells exploit to aggressively proliferate.

IGF2BP3 belongs to a family of RNA-binding proteins typically active only in early human development, after which their expression dramatically decreases. However, in various malignancies such as leukemia, brain tumors, sarcomas, and breast cancers, this protein mysteriously reactivates, driving oncogenic processes. The UCLA group’s prior work demonstrated that IGF2BP3 is indispensable for a highly aggressive subtype of pediatric acute lymphoblastic leukemia, with knockout mouse models resistant to leukemia development without evident health defects. These findings suggested IGF2BP3’s unique role in cancer, spurring further exploration of its impact on cellular energetics.

To interrogate IGF2BP3’s metabolic role, the researchers utilized the sophisticated Seahorse assay technology. This method measures oxygen consumption and extracellular acidification rates, effectively placing cells on a metabolic treadmill to analyze how they utilize energy. Remarkably, leukemia cells deprived of IGF2BP3 showed a profound reduction in glycolysis, indicating that the protein favors rapid sugar catabolism despite its inefficiency in total ATP generation. This metabolic shift ensures a supply of anabolic precursors critical for rapid cell growth, illustrating how IGF2BP3 orchestrates adaptive metabolism tailored to leukemia cells’ survival.

Further metabolic tracing revealed that without IGF2BP3, levels of S-adenosyl methionine (SAM), a universal methyl donor for RNA modifications, plummeted. As RNA methylation is vital for post-transcriptional gene regulation and proper protein synthesis, this finding highlights an elegant feedback loop where IGF2BP3-dependent metabolism affects RNA regulation through epigenetic-like chemical tagging. The diminished RNA methylation marks in IGF2BP3-deficient cells elucidate a previously unrecognized axis linking metabolism directly to RNA function, reshaping the conceptual framework of cancer cell biology.

To validate these molecular insights in vivo, the team engineered mice lacking the IGF2BP3 gene and subsequently introduced the human IGF2BP3 gene. This reintroduction restored the disrupted metabolic and RNA regulatory processes, unequivocally confirming IGF2BP3’s central role in driving the pathological state. This animal model experiment underscores the therapeutic potential of targeting IGF2BP3, as its absence impedes leukemia development while sparing healthy tissue function, making it an attractive candidate for anti-cancer drug development.

Postdoctoral scholar Dr. Gunjan Sharma, a pivotal member of the research team, described the multistep cascade initiated by IGF2BP3 as a “chain reaction.” The protein’s absence reverberated through cellular systems, not only attenuating energy utilization but also altering the chemical and epigenetic landscape governing RNA. This discovery provides a mechanistic explanation for how leukemia cells co-opt metabolic and RNA regulatory networks to maintain their malignant state, offering a holistic target instead of isolated pathways that often lead to drug resistance.

The study’s findings signify that the glycolytic pathway favored by leukemia cells via IGF2BP3 is chosen not for energy efficiency but for its biosynthetic advantage. The swift generation of metabolic intermediates supplies essential building blocks like nucleotides and amino acids, while SAM-driven RNA modifications ensure robust translation of oncogenic proteins. This metabolic rewiring crafts a cancer-specific survival niche, dramatically differentiating malignant cells from their normal counterparts and revealing vulnerabilities that could be exploited therapeutically.

IGF2BP3 thus functions as a molecular architect, simultaneously reshaping energy metabolism and RNA modification machineries to produce an optimal environment for cancer cell endurance and expansion. By coordinating these complex networks, the protein secures leukemia cells’ dominance in hostile conditions that would otherwise suppress normal cell proliferation. This dual regulatory role distinguishes IGF2BP3 from traditional cancer targets that typically affect singular pathways.

While this research filtered through the lens of leukemia, the implications are far-reaching. Similar metabolic and RNA regulatory strategies may be operational across diverse cancer types, including solid tumors like breast cancer and brain cancers where IGF2BP3 is aberrantly expressed. Therefore, insights gained here could inspire broad-spectrum therapies targeting metabolic and post-transcriptional regulatory hubs critical to malignant growth, potentially revolutionizing oncology treatment paradigms.

Moreover, the researchers propose that heightened expression of IGF2BP3 may serve as a diagnostic biomarker, pinpointing cancers that depend on these integrated pathways and identifying patients likely to benefit from therapies aimed at disrupting IGF2BP3’s function or the metabolic networks it controls. This stratification could enhance precision medicine efforts and optimize clinical outcomes in cancer care.

Currently, Rao’s laboratory is advancing small-molecule inhibitors designed to block IGF2BP3 activity. The most effective therapeutic strategies may combine these molecular inhibitors with drugs that directly interfere with cancer metabolism, creating a one-two punch that starves cancer cells energetically and impairs their RNA regulatory machinery. Such combination therapies hold promise for overcoming resistance mechanisms and achieving durable remissions in patients with aggressive leukemia and possibly other IGF2BP3-driven tumors.

The multidisciplinary team contributing to this study spans expertise in molecular biology, metabolism, and translational medicine, including researchers from UCLA and the University of California, Santa Cruz. Supported by grants from the National Institutes of Health and the California Institute for Regenerative Medicine, this collaboration underscores the importance of integrated scientific approaches in unraveling complex cancer biology and moving toward innovative therapies that could save countless lives.

Subject of Research:
Leukemia cell metabolism and RNA regulation linked by IGF2BP3 protein

Article Title:
IGF2BP3: A Master Regulator Linking Metabolic Reprogramming and RNA Modification in Leukemia

News Publication Date:
2025

Web References:
http://dx.doi.org/10.1016/j.celrep.2025.116330

Keywords:
Leukemia, RNA, Metabolism, Cancer, Blood cancer, Cancer cells, Cancer research, Oncology

At its core, the UCLA study draws on longitudinal data to trace how warmth expressed by mothers—characterized by behaviors such as praise, positive tone of voice, and affectionate gestures—translates into more positive social safety schemas in children during their teenage years. These schemas are mental frameworks through which individuals interpret social interactions, predicting the degree to which they perceive the world as safe, supportive, and inclusive. The emergence of these frameworks by age 14 remarkably forecasts their physical and mental health status at age 17, suggesting a powerful targeting point for early intervention and clinical applications.

This research uniquely positions social safety perception as an underlying mechanism driving the correlations long noted between parenting styles and health outcomes. Prior studies have robustly linked maternal warmth with improvements in health across the lifespan, but the precise cognitive or psychological processes remained elusive. The UCLA team’s work bridges this gap by demonstrating that children internalize social experiences into schemas that shape their ongoing interactions with the world. This reframing from direct behavioral influences to the mediation of internalized beliefs revolutionizes approaches focusing on mental health resilience and prevention strategies.

Intriguingly, the research distinguishes the effects of maternal warmth from maternal harshness. Whereas warmth predicted stronger, more positive social safety schemas and associated improvements in health markers, harshness—such as physical restraining or other forms of negative maternal behavior—did not significantly influence children’s later perception of social safety or health outcomes. This suggests that nurturing positive experiences may be substantially more impactful than simply mitigating negative ones, shedding new light on therapeutic priorities and public health messaging.

The conceptualization of social safety schemas marks a critical advance in understanding how early interpersonal dynamics become internalized cognitive structures that filter every subsequent social encounter. As explained by lead author Dr. Jenna Alley, these schemas function as the lens through which individuals view their social environment, forming core beliefs about predictability, acceptance, and support. Such beliefs not only govern emotional wellbeing but also carry neurobiological implications that cascade into physical health consequences through stress-related pathways.

Methodologically, the study capitalized on the vast Millennium Cohort Study in the United Kingdom, leveraging a sample exceeding 8,500 children to ensure robust and generalizable findings. Maternal warmth and harshness were independently assessed at age 3 by trained evaluators during home visits. At age 14, participants completed evaluations measuring their perception of social safety, including questions addressing their sense of support from family and friends. Subsequently, health outcomes—including physical health, psychological distress, and psychiatric symptoms—were self-reported at age 17, enabling comprehensive longitudinal tracking across critical developmental milestones.

These results have rich implications not only for developmental psychology but also for public health strategies aimed at enhancing resilience in youth. The emphasis on fostering social safety perceptions suggests that interventions centered on promoting feelings of inclusion and support may yield long-term physical and mental health benefits, even in populations with histories of early adversity. This strengthens calls for integrating psychological and social dimensions into healthcare and educational systems, moving beyond symptom treatment toward prevention rooted in cognitive schema enhancement.

Moreover, the study highlights a significant research gap concerning paternal warmth. Due to limited data availability, the role of fathers’ caregiving behaviors remains understudied, although initial evidence suggests paternal warmth could likewise shape child outcomes positively. Future research directions must address these gaps, evaluating how both maternal and paternal warmth interplay to influence social safety schema construction and health trajectories. Such comprehensive approaches will better inform family-centered interventions.

UCLA Health’s findings not only highlight the power of early-life positive experiences but also inject a hopeful narrative of resilience. Even children exposed to less-than-ideal maternal care are not irrevocably disadvantaged. By focusing on reshaping their perceptions of the social world, there exists profound potential for altering developmental pathways toward healthier outcomes. This conceptual optimism bolsters ongoing efforts in mental health care emphasizing the plasticity of cognitive frameworks throughout adolescence and beyond.

Senior author Dr. George Slavich underscores the practical import of these insights, noting that enhancing social safety perceptions could transform public health campaigns and therapy models. By emphasizing strengths and fostering warmth, societies can support youth in developing robust psychological shields against future stressors, potentially reducing the burden of psychiatric disorders and chronic physical illnesses. This research thus provides a timely, evidence-based foundation for reimagining how communities nurture their youngest members.

The UCLA study is a clarion call to researchers, clinicians, and policymakers alike to prioritize nurturing social environments in early childhood as integral to holistic health promotion. It advocates for a shift from solely mitigating risk factors toward actively cultivating supportive and affirming experiences. This paradigm shift carries the promise of reducing disease burden, enhancing quality of life, and promoting lifelong resilience grounded in deeply held positive social beliefs.

Looking forward, additional studies will be necessary to validate these findings across diverse cultural and social contexts beyond the UK setting. Cross-cultural investigations will elucidate which aspects of maternal warmth and social safety perception are universally critical versus context-specific, informing targeted adaptations in intervention design. As the neuroscience of social safety schemas continues to evolve, interdisciplinary collaborations will further unravel their biological substrates, enabling precision medicine approaches that tailor psychological and physical health care from an early age.

In sum, this pioneering work at UCLA Health not only elucidates the psychological threads weaving early parental warmth into the fabric of adolescent health but also charts a hopeful, actionable course for enhancing youth wellbeing. By illuminating the centrality of social safety schemas, it redefines our understanding of human development and underscores a fundamental truth: a warm, supportive early environment gives children a vital lens through which to view—and thrive in—the world.

Subject of Research: People

Article Title: Childhood Maternal Warmth, Social Safety Schemas, and Adolescent Mental and Physical Health

News Publication Date: 28-May-2025

Web References:
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2025.0815

DOI link: 10.1001/jamapsychiatry.2025.0815

Keywords: Mental health, Clinical psychology, Psychological stress, Stress management, Psychiatric disorders, Parenting, Family, Behavioral neuroscience

The alterations in liver function resulting from diesel exposure were not trivial; they included an increased production of triglycerides, fatty acids, and sugars. Central to these changes was the dysfunction of mitochondria—an essential organelle responsible for energy production within cells. This mitochondrial dysfunction appears to be a major player in the metabolic disturbances associated with diesel exposure, suggesting that environmental factors can have profound effects on cellular metabolism and overall health.

To delve deeper into the mechanisms at play, the researchers exposed liver cells directly to diesel particles. Their findings indicated that these particles were potent enough to trigger the activation of a specific gene known as Pck1. This gene is crucial for glucose metabolism, and its activation led to heightened levels of glucose production within the liver. Understanding Pck1’s role became a key focus for the researchers, as they sought to elucidate the chain of biochemical events prompted by diesel exposure.

In an effort to explore the functional significance of Pck1, the researchers employed genetic inhibition techniques, which allowed them to effectively reduce glucose levels in the liver cells. This experiment confirmed the gene’s involvement in glucose production, providing compelling evidence that targeting Pck1 might offer a therapeutic avenue for mitigating the adverse metabolic effects of diesel exposure. The methodological rigor of these experiments mentioned earlier paved the way for deeper insights into how air pollutants can trigger specific genetic responses in liver metabolism.

The background of the research illustrates the broader context of air pollution as a significant contributor to various metabolic diseases, including type 2 diabetes and fatty liver disease. Previous investigations by the same team had already established a connection between diesel emissions and mitochondrial dysfunction in liver cells, but this new study represents a notable advancement, demonstrating the in-vivo effects of such exposure in a living organism. The ability to replicate these phenomena in mice brings us closer to understanding the human implications of prolonged exposure to diesel exhaust.

Linking air pollution to metabolic disorders is not entirely new; however, the exact biological mechanisms and genes involved remain shrouded in mystery. The current findings shine a spotlight on the direct impact of diesel particles on liver function, suggesting that the activation of specific genes like Pck1 may play a critical role in the development of metabolic diseases among individuals exposed to diesel exhaust in their daily lives. Given the rising rates of type 2 diabetes and fatty liver disease globally, these findings are particularly relevant for public health discourse.

The implications of this research are profound, as they suggest that the health risks associated with air pollution may extend beyond respiratory ailments to include metabolic disorders. The relationship between air quality and health has garnered attention in recent years, but the details of how specific exposures, such as diesel exhaust, can precipitate conditions like type 2 diabetes are crucial for forming effective public health policies. This research could motivate further investigations into how interventions could mitigate these risks.

Looking towards the future, the researchers express optimism that targeting Pck1 might represent a viable intervention strategy. By providing a molecular target for therapeutic development, this approach could yield new treatments tailored to counteract the metabolic disruptions caused by environmental pollutants. As research continues, understanding the full spectrum of diesel exposure effects will be essential for developing comprehensive strategies aimed at preserving liver health and overall metabolic function.

The study is not merely an academic exercise; it serves as a vital reminder of the everyday risks associated with air pollution. While diesel engines are common in urban environments worldwide, the discovery that they may contribute to significant liver dysfunction and metabolic disorders underscores the need for stricter regulations and policies to mitigate diesel emissions. Advocacy for cleaner air is not just an environmental issue but is intricately linked to public health and wellness.

The significance of this study reverberates beyond scientific circles; it calls for a concerted effort among policymakers, healthcare providers, and communities to prioritize clean air initiatives. Given the tragic consequences of metabolic diseases, which can drastically impact quality of life, finding actionable solutions to air pollution is both an ethical obligation and a public health necessity. Outreach initiatives that educate communities on the health implications of air pollutants can influence public opinion, helping to expedite necessary legislative changes.

In conclusion, the UCLA Health researchers’ work adds compelling evidence to the growing body of research on air pollution and metabolic health. The intricate connections they have unveiled between diesel exhaust, mitochondrial dysfunction, and gene activation pave the way for future investigations into interventions that could potentially alter the health trajectories of millions exposed to diesel emissions. This study not only highlights the urgent need for pollution reductions but also suggests a path forward for targeted therapies aimed at preventing air pollution-induced metabolic disorders.

Subject of Research: Animals
Article Title: Findings on Diesel Exhaust and Liver Function
News Publication Date: October 2023
Web References: 10.1186/s12989-024-00605-6
References: Particle and Fibre Toxicology
Image Credits: N/A

Keywords

Environmental sciences, diesel exhaust, liver function, metabolic disease, mitochondrial dysfunction, air pollution.