Enhancing nutritional niche and host defenses by modifying the gut microbiome

Sun, Qing; Vega, Nicole M.; Cervantes, Bernardo; Mancuso, Christopher P.; Mao, Ning; Taylor, Megan; Collins, James J.; Khalil, Ahmad S.; Gore, Jeff; Lu, Timothy K.

doi:10.15252/msb.20209933

Cited by 9 publications

(5 citation statements)

References 41 publications

(53 reference statements)

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“…One important challenge to specifically target the microbiome with nutritional supplements is to prevent host uptake or metabolization of the supplements 64 . Different approaches to achieve restricted bioavailability, such as the supplementation of non-digestible carbohydrates 65 or coating of supplements with compounds that dissolve during passage through the digestive tract have been developed [66][67][68] .…”

Section: Discussionmentioning

confidence: 99%

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Μαρίνος

Hamerich

Debray

et al. 2023

Preprint

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The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of interest. Moreover, current approaches for microbiome manipulation such as fecal transfers often entail a non-specific transfer of entire microbial communities with potentially unwanted side effects. To overcome this limitation, we here propose the concept of precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In a first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we present a metabolic modeling network framework that allows us to define precision prebiotics for a two-member C. elegans microbiome model community comprising the immune-protective Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. Thus, we predicted compounds that specifically boost the abundance of the host-beneficial MYb11, four of which were experimentally validated in vitro (L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid). L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that constraint-based metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Μαρίνος

Hamerich

Debray

et al. 2023

Preprint

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show abstract

“…8 ). Microbiomes found within gut tissue often provide enzymes that can break down otherwise indigestible carbohydrates ( 53 , 54 ). Moreover, gene expression related to antibiotic biosynthesis presents a direct defense provided by the microbiome against pathogenic bacteria and fungi and the potential for discovering new antibiotics ( 55 , 56 ).…”

Section: Discussionmentioning

confidence: 99%

Microbiome composition and function within the Kellet’s whelk perivitelline fluid

Daniels,

Nurge,

De Smet

et al. 2024

Microbiol Spectr

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This study provides novel insight to an encapsulated system with strong evidence of symbiosis between the microbial inhabitants and developing host embryos. The Kellet’s whelk perivitelline fluid (PVF) contains microbial organisms of interest that may be providing symbiotic functions and potential antimicrobial properties during this vulnerable life history stage. This study, the first to utilize a comprehensive approach to investigating Kellet’s whelk PVF microbiome, couples 16S rRNA gene long-read sequencing with RNA-seq. This research contributes to and expands our knowledge on the roles of beneficial host-associated microbes.

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“…One important challenge to specifically target the microbiome with nutritional supplements is to prevent host uptake or metabolization of the supplements ( 65 ). Different approaches to achieve restricted bioavailability, such as the supplementation of non-digestible carbohydrates ( 66 ) or coating of supplements with compounds that dissolve during passage through the digestive tract have been developed ( 67 – 69 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Marinos,

Hamerich,

Debray

et al. 2024

Microbiol Spectr

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While numerous health-beneficial interactions between host and microbiota have been identified, there is still a lack of targeted approaches for modulating these interactions. Thus, we here identify precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In the first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we use metabolic modeling to identify precision prebiotics for a two-member Caenorhabditis elegans microbiome community comprising the immune-protective target species Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. We experimentally confirm four of the predicted precision prebiotics, L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid, to specifically increase the abundance of MYb11. L-serine was further assessed in vivo , leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies. IMPORTANCE While various mechanisms through which the microbiome influences disease processes in the host have been identified, there are still only few approaches that allow for targeted manipulation of microbiome composition as a first step toward microbiome-based therapies. Here, we propose the concept of precision prebiotics that allow to boost the abundance of already resident health-beneficial microbial species in a microbiome. We present a constraint-based modeling pipeline to predict precision prebiotics for a minimal microbial community in the worm Caenorhabditis elegans comprising the host-beneficial Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71 with the aim to boost the growth of MYb11. Experimentally testing four of the predicted precision prebiotics, we confirm that they are specifically able to increase the abundance of MYb11 in vitro and in vivo . These results demonstrate that constraint-based modeling could be an important tool for the development of targeted microbiome-based therapies against human diseases.

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Enhancing nutritional niche and host defenses by modifying the gut microbiome

Cited by 9 publications

References 41 publications

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Microbiome composition and function within the Kellet’s whelk perivitelline fluid

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

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