Functional Characterization of IgA-Targeted Bacterial Taxa from Undernourished Malawian Children that Produce Diet-Dependent Enteropathy

Andrew L. Kau, Joseph D. Planer, Jie Liu, Sindhuja Rao, Tanya Yatsunenko, Indi Trehan, Mark J. Manary, Ta-Chiang Liu, Thaddeus S. Stappenbeck, Kenneth M. Maleta, Per Ashorn, Kathryn G. Dewey, Eric R. Houpt, Chyi-Song Hsieh and Jeffrey I. Gordon


From left to right: Andrew L. Kau, Jeffrey I. Gordon and Joseph D. Planer

Understanding how the mucosal immune system responds to members of the gut microbiota in infants and children with undernutrition is very important if we are (i) to gain greater knowledge of the pathogenesis of this devastating global health problem, and (ii) identify new ways to achieve effective and durable therapeutic interventions (and ultimately prevent) undernutrition. We have developed a method for recovering the microbial targets of host immunoglobulin A (IgA) responses in a viable form using fluorescence-activated cell sorting.  We apply this method, which we name ‘BugFACS’, to three types of samples: (i) fecal microbiota samples collected from gnotobiotic mice that contain transplanted microbiota from a twin pair discordant for a form of severe acute malnutrition (SAM; kwashiorkor) and that are fed a representative macro- and micronutrient deficient Malawian diet or a nutrient-sufficient healthy diet; (ii) directly to human fecal samples obtained from 11 Malawian twin pairs discordant for kwashiorkor plus eight twin pairs who remained concordant for healthy status during the first three years of life, and (iii) fecal microbiota collected from 6 and 18 month-old Malawian infants with and without stunting. The biological effects of these purified IgA+ consortia, and selected members of these consortia, were defined in gnotobiotic animals fed nutrient-deficient or -sufficient diets, and further characterized by direct culture and sequencing.

Science Translational Medicine 25 Feb 2015: Vol. 7, Issue 276, pp. 276ra24 DOI: 10.1126/scitranslmed.aaa4877