Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges

Abstract Probiotics and live bacterial therapeutics are garnering increased attention for use in human health and have the potential to revolutionise the treatment of gastrointestinal diseases. However, a pervasive feature of bacteria that must be considered in the design of safe and effective probi...

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Main Authors: Julia Leeflang, Josephine A. Wright, Daniel L. Worthley, M. Omar Din, Susan L. Woods
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:npj Biofilms and Microbiomes
Online Access:https://doi.org/10.1038/s41522-025-00734-6
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author Julia Leeflang
Josephine A. Wright
Daniel L. Worthley
M. Omar Din
Susan L. Woods
author_facet Julia Leeflang
Josephine A. Wright
Daniel L. Worthley
M. Omar Din
Susan L. Woods
author_sort Julia Leeflang
collection DOAJ
description Abstract Probiotics and live bacterial therapeutics are garnering increased attention for use in human health and have the potential to revolutionise the treatment of gastrointestinal diseases. However, a pervasive feature of bacteria that must be considered in the design of safe and effective probiotics and live bacterial therapeutics is their capacity for rapid evolution, both at the individual (epi)genetic level and in terms of population dynamics. Here we summarise gastrointestinal-specific evolution of bacteria, focussing on genetic and population levels of adaptation to factors such as carbon source availability, environmental stressors, and interactions with the native microbiome. We also address regulatory and safety considerations for the development of probiotics and live biotherapeutics from an evolutionary perspective, with a discussion of methods that utilise evolution to improve probiotic safety and efficacy via directed evolution, in comparison to another popular approach, genetic engineering.
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series npj Biofilms and Microbiomes
spelling doaj-art-2875a70b67404efcb227ca3c43a9e7542025-08-20T02:31:03ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-06-011111810.1038/s41522-025-00734-6Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challengesJulia Leeflang0Josephine A. Wright1Daniel L. Worthley2M. Omar Din3Susan L. Woods4Adelaide Medical School, University of AdelaidePrecision Cancer Medicine Theme, South Australia Health and Medical Research InstituteColonoscopy ClinicDepartment of Pediatrics, University of California, San DiegoAdelaide Medical School, University of AdelaideAbstract Probiotics and live bacterial therapeutics are garnering increased attention for use in human health and have the potential to revolutionise the treatment of gastrointestinal diseases. However, a pervasive feature of bacteria that must be considered in the design of safe and effective probiotics and live bacterial therapeutics is their capacity for rapid evolution, both at the individual (epi)genetic level and in terms of population dynamics. Here we summarise gastrointestinal-specific evolution of bacteria, focussing on genetic and population levels of adaptation to factors such as carbon source availability, environmental stressors, and interactions with the native microbiome. We also address regulatory and safety considerations for the development of probiotics and live biotherapeutics from an evolutionary perspective, with a discussion of methods that utilise evolution to improve probiotic safety and efficacy via directed evolution, in comparison to another popular approach, genetic engineering.https://doi.org/10.1038/s41522-025-00734-6
spellingShingle Julia Leeflang
Josephine A. Wright
Daniel L. Worthley
M. Omar Din
Susan L. Woods
Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
npj Biofilms and Microbiomes
title Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
title_full Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
title_fullStr Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
title_full_unstemmed Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
title_short Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges
title_sort evolutionary adaptation of probiotics in the gut selection pressures optimization strategies and regulatory challenges
url https://doi.org/10.1038/s41522-025-00734-6
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