Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs

TY - JOUR

T1 - Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs

AU - Brunse, Anders

AU - Martin, Lena

AU - Rasmussen, Torben Sølbeck

AU - Christensen, Lars

AU - Skovsted Cilieborg, Malene

AU - Wiese, Maria

AU - Khakimov, Bekzod

AU - Pieper, Robert

AU - Nielsen, Dennis Sandris

AU - Sangild, Per Torp

AU - Thymann, Thomas

PY - 2019/3/1

Y1 - 2019/3/1

N2 - This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.

AB - This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.

U2 - 10.1038/s41396-018-0301-z

DO - 10.1038/s41396-018-0301-z

M3 - Journal article

C2 - 30367124

AN - SCOPUS:85055686663

SN - 1751-7362

VL - 13

SP - 720

EP - 733

JO - ISME Journal

JF - ISME Journal

ER -