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Quantification of bacterial strain count in the human gut microbiome in health and disease

Award Number: F30DK131862
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/23/2021
PERIOD OF PERFORMANCE END DATE: 12/22/2025

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Quantification of bacterial strain count in the human gut microbiome in health and disease - PROJECT SUMMARY In Inflammatory Bowel Disease (IBD), the gut microbiome demonstrates reduced species diversity that can then be reversed following FMT. However, no study has identified a common pattern of microbiome alteration that is causally related to IBD nor has any study elucidated the mechanisms underlying FMT success in the subset of individuals with IBD that respond. In FMT, both species and strain diversity are increasing but currently studies only track changes in species diversity, resulting in a fundamental feature of the microbiome that is changing but not measured in trials or in cross sectional studies of comparing with healthy and IBD microbiomes. Thus, it is unclear whether it is the increase in species or strain diversity that is critical to FMT success or if there are unique differences in the strain-level structure of the IBD microbiome. Since microbial functional variation is found at the strain level, a functional understanding of microbiome composition in IBD may lie at the strain level. However, no studies so far have systematically characterized the strain-level microbiome structure in health or disease. This proposal aims to define strain count—the number of unique strains each bacterial species stably maintains in an individual—in healthy and IBD microbiomes and to further investigate the functional impact of strain count in disease. We will quantify strain count by employing a high- throughput culturing technique to isolate and sequence thousands of gut bacterial isolates for all culturable species in a breadth-focused manner and validate our breadth-focused quantifications by using a depth- focused approach to intensely sequence more genomes from ten of the most common gut species. For our depth-sequencing, we will use gnotobiotic mice fed different diets to enrich for low abundance strains. This experimental approach allows us to increase the efficiency by which we capture the strains of a particular species and achieve a more accurate quantification of strain count. Aim 1—Based on our preliminary findings, we anticipate that there is a limited number of strains each species can maintain in the gut microbiota and that our method sequences a sufficient number of genomes to quantify strain count. We aim to define strain count in healthy and IBD microbiomes which will allow for higher resolution, functional investigations into microbiome composition in disease. In Aim 2—we will investigate the effect of increasing strain count on colitis severity. We will combine defined communities of strains isolated from an IBD and healthy microbiota in a gnotobiotic T cell transfer colitis model. The defined communities will allow us to specifically increase strain count while holding species diversity stable. By studying the functional role of strain count, we can uncover the potential contributions of microbiome strain-level architecture to the disease process and identify appropriate targets for optimizing FMT for the treatment of IBD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2027 ( Subtotal = -$9,042 )
2027	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	10/27/2026	NON-COMPETING CONTINUATION	-$9,042
														Subtotal = -$9,042

Issue Date FY: 2025 ( Subtotal = $54,244 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	5/29/2025	NON-COMPETING CONTINUATION	$564
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/25/2024	NON-COMPETING CONTINUATION	$53,680
														Subtotal = $54,244

Issue Date FY: 2024 ( Subtotal = $47,374 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/8/2023	NON-COMPETING CONTINUATION	$46,094
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/29/2024	NON-COMPETING CONTINUATION	$1,280
														Subtotal = $47,374

Issue Date FY: 2023 ( Subtotal = $47,534 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/12/2022	NON-COMPETING CONTINUATION	$46,592
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/17/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $47,534

Issue Date FY: 2022 ( Subtotal = $49,472 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/23/2021	NEW	$48,756
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	12/23/2021	NEW	$0
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	5/10/2022	NEW	$717
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	1	7/8/2022	NEW	-$1
														Subtotal = $49,472

Grand Total All Awards = $189,582

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Quantification of bacterial strain count in the human gut microbiome in health and disease

Award Number: F30DK131862

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/23/2021

PERIOD OF PERFORMANCE END DATE: 12/22/2025

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