title: Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice.
abstract: OBJECTIVE
  Beneficial microbes and probiotics are promising agents for the prevention and treatment of enteric and diarrheal diseases in children; however, little is known about their in vivo mechanisms of action. We used a neonatal mouse model of rotavirus diarrhea to gain insight into how probiotics ameliorate acute gastroenteritis.
  
  
  METHODS
  Rotavirus-infected mice were treated with 1 of 2 strains of human-derived Lactobacillus reuteri. We assessed intestinal microbiome composition with 16S metagenomic sequencing, enterocyte migration and proliferation with 5-bromo-2'-deoxyuridine, and antibody and cytokine concentrations with multiplex analyses of intestinal explant cultures.
  
  
  RESULTS
  Probiotics reduced diarrhea duration, improved intestinal histopathology, and enhanced intestinal microbiome richness and phylogenetic diversity. The magnitude of reduction of diarrhea by probiotics was strain specific and influenced by nutritional status. L reuteri DSM 17938 reduced diarrhea duration by 0, 1, and 2 days in underweight, normal weight, and overweight pups, respectively. The magnitude of reduction of diarrhea duration correlated with increased enterocyte proliferation and migration. Strain ATCC PTA 6475 reduced diarrhea duration by 1 day in all of the mice without increasing enterocyte proliferation. Both probiotic strains decreased concentrations of proinflammatory cytokines, including macrophage inflammatory protein-1α and interleukin-1β, in all of the animals, and increased rotavirus-specific antibodies in all but the underweight animals. Body weight also influenced the host response to rotavirus, in terms of diarrhea duration, enterocyte turnover, and antibody production.
  
  
  CONCLUSIONS
  These data suggest that probiotic enhancement of enterocyte proliferation, villus repopulation, and virus-specific antibodies may contribute to diarrhea resolution, and that nutritional status influences the host response to both beneficial microbes and pathogens.
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Preidis
authors.forename: Delphine M
authors.initials: DM
authors.lastname: Saulnier
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Blutt
authors.forename: Toni-Ann
authors.initials: TA
authors.lastname: Mistretta
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Riehle
authors.forename: Angela M
authors.initials: AM
authors.lastname: Major
authors.forename: Susan F
authors.initials: SF
authors.lastname: Venable
authors.forename: James P
authors.initials: JP
authors.lastname: Barrish
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Conner
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000097:blood; D001835:Body Weight; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D020895:Enterocytes / Q000473:pathology; D005759:Gastroenteritis / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D052200:Limosilactobacillus reuteri; D054892:Metagenome / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D009752:Nutritional Status; D050177:Overweight / Q000150:complications; D010802:Phylogeny; D019936:Probiotics; D012401:Rotavirus; D012400:Rotavirus Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D013851:Thinness / Q000150:complications
chemical_list: D000906:Antibodies; D016207:Cytokines; D018836:Inflammation Mediators