In vitro competition with Bifidobacterium strains impairs potentially pathogenic growth of Clostridium perfringens on 2'-fucosyllactose.

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Název: In vitro competition with Bifidobacterium strains impairs potentially pathogenic growth of Clostridium perfringens on 2'-fucosyllactose.
Autoři: Nakajima A; Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Arzamasov AA; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Sakanaka M; Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Murakami R; Innovative Research Institute, Morinaga Milk Industry Co, Ltd, Zama, Kanagawa, Japan., Kozakai T; Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Yoshida K; Innovative Research Institute, Morinaga Milk Industry Co, Ltd, Zama, Kanagawa, Japan., Katoh T; Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Ojima MN; Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Hirose J; Department of Food and Nutrition, Kyoto Women's University, Kyoto, Japan., Nagao S; Nagao Midwife Clinic, Kyoto, Japan., Xiao JZ; Graduate School of Biostudies, Kyoto University, Kyoto, Japan.; Innovative Research Institute, Morinaga Milk Industry Co, Ltd, Zama, Kanagawa, Japan., Odamaki T; Graduate School of Biostudies, Kyoto University, Kyoto, Japan.; Innovative Research Institute, Morinaga Milk Industry Co, Ltd, Zama, Kanagawa, Japan., Rodionov DA; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Katayama T; Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Zdroj: Gut microbes [Gut Microbes] 2025 Dec; Vol. 17 (1), pp. 2478306. Date of Electronic Publication: 2025 Mar 18.
Způsob vydávání: Journal Article
Jazyk: English
Informace o časopise: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101495343 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1949-0984 (Electronic) Linking ISSN: 19490976 NLM ISO Abbreviation: Gut Microbes Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience
Výrazy ze slovníku MeSH: Clostridium perfringens*/growth & development , Clostridium perfringens*/metabolism , Clostridium perfringens*/genetics , Clostridium perfringens*/pathogenicity , Bifidobacterium*/metabolism , Bifidobacterium*/growth & development , Trisaccharides*/metabolism, Humans ; Infant ; Bacterial Toxins/genetics ; Bacterial Toxins/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome ; Milk, Human/chemistry ; Type C Phospholipases/genetics ; Type C Phospholipases/metabolism ; Coculture Techniques ; Infant Formula/chemistry ; Lactose/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Calcium-Binding Proteins
Abstrakt: Fortifying infant formula with human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), is a global trend. Previous studies have shown the inability of pathogenic gut microbes to utilize 2'-FL. However, the present study demonstrates that the type strain (JCM 1290 T ) of Clostridium perfringens , a pathobiont species often more prevalent and abundant in the feces of C-section-delivered infants, exhibits potentially pathogenic growth on 2'-FL. The expression of genes for α-toxin, an activator of NLRP3 inflammasome, and ethanolamine ammonia-lyase, a factor responsible for the progression of gas gangrene, was significantly upregulated during 2'-FL assimilation compared to growth on lactose. However, colony-forming unit of C. perfringens JCM 1290 T markedly decreased when co-cultivated with selected strains of Bifidobacterium , a taxon frequently detected in the breastfed infant gut. Moreover, during co-cultivation, the expression of virulence-related genes, including the gene for perfringolysin O - another activator of NLRP3 inflammasome - were significantly downregulated, while the lactate oxidation genes were upregulated. This can occur through two different mechanisms: direct competition for 2'-FL between the two organisms, or cross-feeding of lactose, released from 2'-FL by C. perfringens JCM 1290 T , to Bifidobacterium . Attenuation of α-toxin production by the selected Bifidobacterium strains was observed to varying extents in 2'-FL-utilizing C. perfringens strains clinically isolated from healthy infants. Our results warrant detailed in vivo studies using animal models with dysbiotic microbiota dominated by various types of C. perfringens strains to further validate the safety of 2'-FL for clinical interventions, particularly on vulnerable preterm infants.
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Contributed Indexing: Keywords: 2'-fucosyllactose; Bifidobacteria; Clostridium perfringens; α-toxin
Substance Nomenclature: 0 (Trisaccharides)
XO2533XO8R (2'-fucosyllactose)
0 (Bacterial Toxins)
EC 3.1.4.3 (alpha toxin, Clostridium perfringens)
EC 3.1.4.- (Type C Phospholipases)
J2B2A4N98G (Lactose)
0 (Bacterial Proteins)
0 (Calcium-Binding Proteins)
Entry Date(s): Date Created: 20250319 Date Completed: 20250513 Latest Revision: 20250513
Update Code: 20250514
PubMed Central ID: PMC11956901
DOI: 10.1080/19490976.2025.2478306
PMID: 40102238
Databáze: MEDLINE
Popis
Abstrakt:Fortifying infant formula with human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), is a global trend. Previous studies have shown the inability of pathogenic gut microbes to utilize 2'-FL. However, the present study demonstrates that the type strain (JCM 1290 <sup>T</sup> ) of Clostridium perfringens , a pathobiont species often more prevalent and abundant in the feces of C-section-delivered infants, exhibits potentially pathogenic growth on 2'-FL. The expression of genes for α-toxin, an activator of NLRP3 inflammasome, and ethanolamine ammonia-lyase, a factor responsible for the progression of gas gangrene, was significantly upregulated during 2'-FL assimilation compared to growth on lactose. However, colony-forming unit of C. perfringens JCM 1290 <sup>T</sup> markedly decreased when co-cultivated with selected strains of Bifidobacterium , a taxon frequently detected in the breastfed infant gut. Moreover, during co-cultivation, the expression of virulence-related genes, including the gene for perfringolysin O - another activator of NLRP3 inflammasome - were significantly downregulated, while the lactate oxidation genes were upregulated. This can occur through two different mechanisms: direct competition for 2'-FL between the two organisms, or cross-feeding of lactose, released from 2'-FL by C. perfringens JCM 1290 <sup>T</sup> , to Bifidobacterium . Attenuation of α-toxin production by the selected Bifidobacterium strains was observed to varying extents in 2'-FL-utilizing C. perfringens strains clinically isolated from healthy infants. Our results warrant detailed in vivo studies using animal models with dysbiotic microbiota dominated by various types of C. perfringens strains to further validate the safety of 2'-FL for clinical interventions, particularly on vulnerable preterm infants.
ISSN:1949-0984
DOI:10.1080/19490976.2025.2478306