NEW $50M Program
Foundations of a Resilient Microbiome
Download the full program announcement here.
The human gut microbiome functions as a vital organ, playing a central role in physiology and health. Increasingly, we understand how central its role is in nutrition and metabolism[i], endocrine regulation, immune system development[ii], as well as its links to neurological, cognitive, and behavioral outcomes[iii]. There are now well-known biochemical pathways, precursors to neurotransmitters, and immune system signals linking the gut microbiome to development and function in every major physiological system of the human body.
In FORM, we are focused on the role of the maternal and developing infant gut microbiome in healthy infant neurodevelopment. Critically, FORM seeks to identify whether an accumulating set of early-life pressures to the developing gut microbiome is one contributing factor to the rise in one form of neurodevelopmental challenge — namely, autism spectrum disorder (ASD). And further, whether resilience to functional disruption can be measured and supported in key developmental windows as a pathway towards reducing the number of children who could go on to experience severe autism-related difficulties.
Forming a Resilient Microbiome. From birth through to age 2, the infant gut microbiome is rapidly forming and reshaping its community and core functions. In this period, everyday environmental exposures and common medical practices impact the formation and function of the infant gut microbiome at different times- some building resilience, others creating stress. For example, birth mode (vaginal or caesarean birth, including whether antibiotics are used) and breastfeeding impact microbiome formation most in the first 6 months; maternal microbiota, solid foods, antibiotics, and family and caregiving environments matter most from 6 months old through to age 2; and maternal factors, such as infection and antibiotic exposure, diet, body mass index, and gestational diabetes impact the maternal microbiome and early infant microbiome throughout the whole period[i]. Importantly, the maternal microbiome itself shifts markedly in the third trimester[ii], affecting microbial transmission at birth and in early life — underscoring the need to see pregnancy and infancy as a connected system for healthy infant microbiome formation. By the end of this multifaceted, formative period, the infant gut microbiome starts to stabilize and approach adult-like maturity. By age 2, the infant gut microbiome has provided signals critical to immune, metabolic and neurodevelopment. The developmental trajectory and resilience of the infant gut microbiome from birth to age 2 has been shown to predict key aspects of a child’s later immune and metabolic health[iv] [iii]. These developmental trajectories are determined by a combination of environmental exposures and early life challenges acting together that can shape or disrupt function of the microbiome[i]. Increasing evidence also suggests that the formation and resilience of both the maternal and infant gut microbiome are key drivers of a child’s brain and cognitive development during this window. Notable work in animal models has demonstrated that:
- Maternal high fat diet during pregnancy and lactation alters the offspring’s microbiome, leading to changes in key neural connections in the brain and social behavior in male pups[iv];
- Maternal immune activation and maternal antibiotic exposure during pregnancy can disrupt the maternal microbiome and circulating metabolites, driving differences in fetal brain development and some autism-like behaviors in animal offspring[v] [vi];
- Different gut microbiomes from infants in the first year of life can drive functional differences in social, cognitive, and executive-function-related behaviors when these human microbiomes are transferred to germ free mice, with effects mediated by a microbiome-driven metabolic disorder (Unpublished data from the Wellcome Leap First 1000 days program).
Across all of these studies, early targeted intervention with key microbial strains or metabolites indicated that it is possible to restore metabolic balance and minimize severe behavioural challenges in animal models (such as atypical social interactions; repetitive behaviors; anxiety like phenotypes and vocalisations). This suggests the potential for interventions to reduce the severity of neurodevelopmental challenges during critical developmental windows, prior to age 2.
Taken together, these findings indicate that the infant gut microbiome functions much like a vital developing organ, shaping early brain and cognitive development while also guiding immune and metabolic health.
To achieve the goals of the program we seek advances in 3 thrust areas.
To test if the gut microbiome is a missing link and determine if we can meet the requirements of a solution with the potential to reduce the number of children experiencing severe autism-related difficulties by 75%, we need advances coordinated across three thrust areas.
- Thrust 1: Identify the proportion of children experiencing ASD attributable to gut microbiome dysfunction, with >90% balanced accuracy, and identify what combination(s) of early life pressures (and when) drive the specific microbiome dysfunction influencing neurodevelopment.
- Thrust 2: Develop objective and scalable methods to: 1) screen the functional contribution of the maternal and infant gut microbiome to infant neurodevelopment to predict cognitive, language, social and executive function challenges, aiming for >70% accuracy; and 2) diagnose a gut microbiome-based functional disorder or disorders predictive of severe autism-related difficulties with >90% accuracy. These performance metrics are comparable to existing early ASD screens like M-CHAT, and sufficient to trigger referral for formal diagnosis, with the clinical grade accuracies expected for a diagnostic test for ASD and other metabolic disorders that result in neurodevelopmental challenges.
- Thrust 3: Pair diagnostic tests with strategies to protect, preserve and restore gut microbiome functions and resilience — in pregnancy and infancy — aiming for >80% effectiveness to support healthy neurodevelopment. Test whether this can meet the requirements of a solution with the potential to reduce the number of new cases of severe autism-related difficulties by 75%.
Advances across thrusts will inform each other to improve and validate screening methods, diagnostic biomarkers, and restoration strategies. It is not necessary to form large consortiums or teams to accomplish all the thrust goals. Synergies and integrated system demonstrations will be facilitated by Wellcome Leap on an annual basis as we make progress together towards the program goal.
Program Director.
Call for abstracts and proposals.
We are soliciting abstracts and proposals for work over three (3) years in one or more of the following thrust areas (see Thrust areas in full program description). Proposers should clearly relate work in these thrust areas to one or more of the program goals.
It is not necessary to form a large consortium or teams to address all facets of the program. The strength of this approach will manifest through program-level integration of efforts from individuals and small agile teams with deep (and sometimes narrow) expertise. Across all projects, Wellcome Leap will facilitate iterative and collaborative integration of findings to refine models and improve and validate predictive measures and adapt approaches as teams make progress towards shared goals.
30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT
31 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK
25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.
All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.
Who is eligible?
Performers from universities and research institutions: small, medium, and large companies (including venture-backed); and government or non-profit research organizations are invited to propose.
Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.
I understand that the information being disclosed will be reviewed and evaluated independently on behalf of Leap. I am submitting information with the intention that it imposes no confidentiality obligations on Leap. Furthermore, my submission does not breach any confidentiality obligations that I owe to others; there is no legal reason why I cannot submit information; and I am not underage or otherwise legally incompetent. By submitting, I am not granting, other than for the purpose of evaluation, any rights in relation to any patent, copyright, or design. I am not relying upon Leap in any way for legal advice, including (but not limited to) whether the contents of my submission can be protected under IP law. I recognize that Leap may already be aware of or funding the same or related efforts as described by my submission. I agree that no contractual obligation or working relationship is being created between myself and Leap by submitting this information. If the submission is deemed of interest, I may be required to sign a further Agreement with Leap so that any confidential information, that is subsequently shared, is protected.
I acknowledge and consent to the use of AI systems operated by third parties, which may be used to process the content of the application. These systems may be used to generate summaries, perform checks, or otherwise assess the application content. The results of such processing may be considered by staff as part of the decision making process. I waive any claims against Wellcome Leap related to the use of AI for such purposes, provided that complies with applicable laws and internal policies.
Abstract application steps.
- Download guidelines
- Download abstract template (and cost and schedule template)
- We’ll remind you when the application portal opens on 7 November 2025 at 11:59pm ET.
- Upload your abstract and submit your application before 14 November 2025 at 11:59pm ET.
Send inquiries to form@wellcomeleap.org
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