Download the full program announcement here. (updated 14 Nov 2025)
Download the FORM Partnership and Trust Principles 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.
Today, there is much scientific debate about results suggesting a link between the early-life microbiome and neurodevelopmental challenges, including autism. There is, however, little debate that more research is needed. In FORM, we are focused on research to better assess 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 could be one contributing factor to the rise in neurodevelopmental challenges — including, autism spectrum disorder (ASD). And further, whether resilience to functional disruption can be measured and supported in key developmental windows and increase options for support as a pathway towards reducing the likelihood of children experiencing severe autism-related difficulties that impact their daily life.
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[iv]. Importantly, the maternal microbiome itself shifts markedly in the third trimester[v], 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] [vi]. 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 may be 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[vii];
- 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[viii] [ix];
- 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 behavioral challenges in animal models (such as atypical social interactions; repetitive behaviors; anxiety like phenotypes and vocalizations). This suggests the future potential for developing 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 may function much like a vital developing organ, potentially 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, we need advances coordinated across 3 thrust areas.
- Thrust 1: Determine whether and to what extent differences in gut microbiome function are causally linked to neurodevelopmental outcomes, including severe autism-related difficulties. This will require identifying the proportion (if any) of ASD cases attributable to early-life microbiome dysfunction with >90% balanced accuracy and defining which combinations of early-life pressures — and in what developmental windows — most strongly influence functions needed for healthy neurodevelopment.
- Thrust 2: Develop scalable methods that can objectively assess the functional contribution of the maternal and infant gut microbiome to infant neurodevelopment. This includes: 1) screening tools to predict risk of cognitive, language, social, and executive function challenges, aiming for >70% accuracy; and 2) diagnostic methods capable of identifying a gut microbiome-based functional disorder or disorders that may be predictive of severe neurodevelopmental, autism-related difficulties with >90% accuracy. These performance metrics are comparable to existing early ASD screens like M-CHAT and would be sufficient to trigger referral for formal diagnosis, with the clinical grade accuracies expected for a diagnostic test for ASD (provided, of course, a causal role is established) 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 could meet the requirements of a solution with the potential to reduce — by 75% — the likelihood of children experiencing severe autism-related difficulties, that may be microbiome attributable.
Advances across thrusts are expected to accelerate progress, inform each other, create the multi-disciplinary teams and effort to challenge results, prove or disprove causation, and do so at convincing scale. Such coordinated activities will also help to develop 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 announcement). Proposers should clearly relate work in these thrust areas to one or more of the program goals. At the abstract stage, applicants will be asked to acknowledge that they will adhere to the FORM Partnership and Trust Principles and address them in their proposal at the full-proposal stage.
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.
Applicants submitting a full proposal may provide proprietary or confidential information. The applicant agrees that they have all necessary rights to make the submission, including rights to disclose all included data and any confidential or proprietary information. If any third party information is included, it is the Applicant’s obligation to ensure that the third party has agreed to these terms.
For information designated as confidential in a submitted full proposal, Wellcome Leap agrees to the following:
- Purpose Limitation: Wellcome Leap will use the confidential information solely for the purpose of reviewing and evaluating the proposal. Such information will not be used for Wellcome Leap’s direct or indirect personal or financial benefit, nor made available for the direct or indirect benefit of any other organization or individual. The applicant acknowledges that any feedback or review received from Wellcome Leap is not legal advice and the applicant will not rely on the same for any action, including on whether or not any IP filings could be made.
- Access Controls and Confidentiality Commitments: Wellcome Leap will not disclose confidential information to anyone except individuals who: (i) have been formally designated by Wellcome Leap to participate in the proposal review; and (ii) are bound by appropriate confidentiality obligations. Wellcome Leap will take reasonable measures at least equivalent to those used to protect its own confidential information to safeguard designated confidential information. Wellcome Leap will promptly notify the applicant of any actual or suspected misuse, misappropriation, or unauthorized disclosure that comes to its attention.
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Exceptions: Wellcome Leap shall have no obligation or liability with respect to information that it can demonstrate:
(i) was in the public domain at the time of disclosure or enters the public domain through no fault of Wellcome Leap;
(ii) was known to Wellcome Leap, without restriction, prior to disclosure;
(iii) is disclosed with the applicant’s prior written consent;
(iv) becomes known to Wellcome Leap, without restriction, from a source not in breach of any confidentiality obligation; or
(v) is required to be disclosed by law, regulation, or court/administrative order, provided that Wellcome Leap will give prompt notice to the applicant to allow the applicant to seek protective measures to limit such disclosure. - Acknowledgment of Similar Efforts: As acknowledged at the abstract stage, the applicant understands that Wellcome Leap may already be aware of, considering, or funding programs or proposals similar to, or overlapping with, the submitted work. Confidentiality obligations under this section do not restrict Wellcome Leap’s ability to pursue such existing or independent efforts so long as Wellcome Leap does not use the applicant’s designated confidential information in doing so.
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Duration
Wellcome Leap’s obligations with respect to designated confidential information will continue for three (3) years from the date the proposal is received. -
Use of AI Systems
Consistent with the abstract-stage acknowledgment, the applicant agrees that Wellcome Leap may use third-party AI systems to assist in processing, summarization, or other assessments of proposal materials. The results of processing may be used by Wellcome Leap as part of its evaluation processes. Any confidential information processed will remain subject to the protections described in this section. To the extent consistent with applicable laws and policies, the applicant waives any claims against Wellcome Leap related to use of AI for these purposes.
No contractual obligation or working relationship is being created between the applicant and Wellcome Leap due to this submission. Any engagement between Wellcome Leap and the applicants will be through separately executed contracts, including master agreements that have been or will be entered into between the parties. Other than the right for Wellcome Leap and its agents to store, copy and modify the submissions for the purpose of evaluation, no rights in relation to any patent, copyright, or design are granted by virtue of this submission.
Full proposal application steps.
- Download guidelines
- Download full proposal template (and cost and schedule template)
- We’ll remind you when the application portal opens on 19 December 2025 at 11:59pm ET.
- Upload your full proposal and submit your application before 29 December 2025 at 11:59pm ET.
Send inquiries to form@wellcomeleap.org
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