دورية أكاديمية
A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism.
العنوان: | A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism. |
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المؤلفون: | Schalich KM; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Buendia MA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Kaur H; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Choksi YA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Washington MK; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Codreanu GS; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.; Center for Innovative Technology, Vanderbilt University, Nashville, Tennessee, USA., Sherrod SD; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.; Center for Innovative Technology, Vanderbilt University, Nashville, Tennessee, USA., McLean JA; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.; Center for Innovative Technology, Vanderbilt University, Nashville, Tennessee, USA., Peek RM Jr; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Acra SA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Townsend SD; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA., Yan F; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA. |
المصدر: | MBio [mBio] 2024 Apr 10; Vol. 15 (4), pp. e0029824. Date of Electronic Publication: 2024 Mar 05. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
مواضيع طبية MeSH: | Gastrointestinal Microbiome* , Colitis, Ulcerative*/metabolism , Colitis*/prevention & control, Pantothenic Acid/*analogs & derivatives, Adult ; Humans ; Animals ; Mice ; Milk, Human ; Oligosaccharides/metabolism ; Inflammation |
مستخلص: | Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2'-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption. Here, we investigated how 2'-FL prevents colitis in adulthood through its effects on the gut microbial community. We found that the gut microbiota from adult mice that consumed 2'-FL exhibited an increase in abundance of several health-associated genera, including Bifidobacterium and Lactobacillus . The 2'-FL-modulated gut microbial community exerted preventive effects on colitis in adult mice. By using Bifidobacterium infantis as a 2'-FL-consuming bacterial model, exploratory metabolomics revealed novel 2'-FL-enriched secretory metabolites by Bifidobacterium infantis , including pantothenol. Importantly, pantothenate significantly protected the intestinal barrier against oxidative stress and mitigated colitis in adult mice. Furthermore, microbial metabolic pathway analysis identified 26 dysregulated metabolic pathways in fecal microbiota from patients with ulcerative colitis, which were significantly regulated by 2'-FL treatment in adult mice, indicating that 2'-FL has the potential to rectify dysregulated microbial metabolism in colitis. These findings support the contribution of the 2'-FL-shaped gut microbial community and bacterial metabolite production to the protection of intestinal integrity and prevention of intestinal inflammation in adulthood.IMPORTANCEAt present, neither basic research nor clinical studies have revealed the exact biological functions or mechanisms of action of individual oligosaccharides during development or in adulthood. Thus, it remains largely unknown whether human milk oligosaccharides could serve as effective therapeutics for gastrointestinal-related diseases. Results from the present study uncover 2'-FL-driven alterations in bacterial metabolism and identify novel B. infantis -secreted metabolites following the consumption of 2'-FL, including pantothenol. This work further demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice. Remarkably, 2'-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients. These novel metabolic pathways underlying the bioactivities of 2'-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis. Competing Interests: The authors declare no conflict of interest. |
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معلومات مُعتمدة: | T32 DK007673 United States DK NIDDK NIH HHS; R01 CA077955 United States CA NCI NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; P01 CA116087 United States CA NCI NIH HHS; R01 DK058587 United States DK NIDDK NIH HHS; R35 GM133602 United States GM NIGMS NIH HHS; IK2 BX004648 United States BX BLRD VA; R01 DK081134 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: 2′-fucosyllactose; Bifidobacterium longum subsp. infantis; human milk oligosaccharide; inflammatory bowel diseases; intestinal barrier; pantothenate; the gut microbiota |
المشرفين على المادة: | 1O6C93RI7Z (dexpanthenol) 0 (Oligosaccharides) 19F5HK2737 (Pantothenic Acid) |
تواريخ الأحداث: | Date Created: 20240305 Date Completed: 20240411 Latest Revision: 20240429 |
رمز التحديث: | 20240430 |
مُعرف محوري في PubMed: | PMC11005405 |
DOI: | 10.1128/mbio.00298-24 |
PMID: | 38441000 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2150-7511 |
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DOI: | 10.1128/mbio.00298-24 |