TY - JOUR
T1 - From fecal microbiota transplantation toward next-generation beneficial microbes
T2 - The case of Anaerobutyricum soehngenii
AU - Wortelboer, Koen
AU - Koopen, Annefleur M.
AU - Herrema, Hilde
AU - de Vos, Willem M.
AU - Nieuwdorp, Max
AU - Kemper, E. Marleen
N1 - Funding Information: KW was supported by a Novo Nordisk Foundation CAMIT grant 2018 (28232). HH was supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (2019.82.004). WV was supported by the Netherlands Organization for Scientific Research (Spinoza Award and SIAM Gravity Grant 024.002.002). MN was supported by a personal ZONMW-VICI grant 2020 (09150182010020) and a Le Ducq consortium grant (17CVD01). Publisher Copyright: Copyright © 2022 Wortelboer, Koopen, Herrema, de Vos, Nieuwdorp and Kemper.
PY - 2022/12/5
Y1 - 2022/12/5
N2 - The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.
AB - The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.
KW - Anaerobutyricum soehngenii
KW - Eubacterium hallii
KW - fecal microbiota transplantation
KW - live biotherapeutic product
KW - next-generation probiotic
UR - http://www.scopus.com/inward/record.url?scp=85144166676&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fmed.2022.1077275
DO - https://doi.org/10.3389/fmed.2022.1077275
M3 - Review article
C2 - 36544495
SN - 2296-858X
VL - 9
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 1077275
ER -