Lukacs Laboratory

Home Lab Members Dendritic Cell Biology Early Life RSV Infection Epigenetics Mast Cell Biology & SCF Microbiome Contact Information
  1. Home
  2. Microbiome

Microbiome

The effect of changes in the microbiome on allergic responses is a well-documented phenomenon associated with changes in the trajectory and development of immune responses, especially during infancy when the microbiome is initially established. Previous studies have established that severe RSV infected infants have a dysbiotic microbiome compared to uninfected (see below). Recent studies on how microbiome-derived metabolites can regulate inflammation and immune responses have become an intense area of research and help explain the link between microbiome and immune development. Increases in a broad range of microbial- and/or mammalian-derived lipids, amino acids, and peptides with immunomodulatory potential, support that metabolic signaling may be an important mechanism by which the microbiome and host interact.  A link between diet and microbiome for regulation of immune responses has been established between dietary fiber intake and presence of Clostridiales, leading to production of short chain fatty acids (SCFA) and development of Treg cells. Furthermore, polyunsaturated fatty acids (PUFA) and SCFA reduce adhesion molecule expression and cytokine production by reducing inflammasome activation. Our own recent work suggests that altering the microbiome by the addition of Lactobacilli promotes a favorable bacterial community and gives rise to increased regulatory lipid metabolites, including PUFA, that regulate immune responses (see below). The initial responses are now thought to include significant influence by the commensal microbiome, wherein the gut appears to be most important, for both maturing the immune system and providing an appropriate tolerogenic environment.  Early perturbation of the microbiome and/or pathogens, such as RSV, may alter the normal/most appropriate progression of immune maturation. The evolving neonatal immune responses are central to controlling the development of childhood allergic disease. The immune responses that are initiated during infancy are important for the long-term health and response to subsequent antigens (pathogenic and environmental) later in life. Using our relevant and innovative modeling we will assess how these mechanisms impact long-term immune responses including allergic outcomes, thus contributing novel information, and setting up new paradigms to be tested.

 

Cecum from uninfected or EL-RSV infected mice were harvested at 8- or 28-days post-infection and subjected to 16s sequencing and analyzed as indicated. The PCA plots (A,B) indicated significant differences and the rank abundance (C,D) identified the modified OTU. Each dot is a separate mouse.
Relative metabolite levels from EL-RSV infected mice and those supplemented with L. johnsonii. Plasma was collected at 8d post-EL-RSV and metabolites measured. (B&C) Red and Pink boxes are those metabolites significant increased (P<0.01 & 0.05) and Blue decreased at 8 days post EL-RSV compared to uninfected.

 

Publications

  1. Panzer AR, Sitarik AR, Fadrosh D, Havstad SL, Jones K, Davidson B, Finazzo S, Wegienka GR, Woodcroft K, Lukacs NW, Levin AM, Ownby DR, Johnson CC, Lynch SV, Zoratti EM. The impact of prenatal dog keeping on infant gut microbiota development. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2023; 53: 833-845.
  2. Asai N, Ethridge AD, Fonseca W, Yagi K, Rasky AJ, Morris SB, Falkowski NR, Huang YJ, Huffnagle GB, Lukacs NW. A steroid-resistant cockroach allergen model is associated with lung and cecal microbiome changes. Physiological reports 2023; 11: e15761.
  3. Yagi K, Asai N, Huffnagle GB, Lukacs NW, Fonseca W. Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection. Frontiers in immunology 2022; 13: 877771.
  4. Joseph CL, Sitarik AR, Kim H, Huffnagle G, Fujimura K, Yong GJM, Levin AM, Zoratti E, Lynch S, Ownby DR, Lukacs NW, Davidson B, Barone C, Cole Johnson C. Infant gut bacterial community composition and food-related manifestation of atopy in early childhood. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2022; 33: e13704.
  5. Fonseca W, Malinczak CA, Fujimura K, Li D, McCauley K, Li J, Best SKK, Zhu D, Rasky AJ, Johnson CC, Bermick J, Zoratti EM, Ownby D, Lynch SV, Lukacs NW, Ptaschinski C. Maternal gut microbiome regulates immunity to RSV infection in offspring. The Journal of experimental medicine 2021; 218.
  6. Michels KR, Lukacs NW, Fonseca W. TLR Activation and Allergic Disease: Early Life Microbiome and Treatment. Current allergy and asthma reports 2018; 18: 61.
  7. Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal immunology 2017; 10: 299-306.
  8. Levin AM, Sitarik AR, Havstad SL, Fujimura KE, Wegienka G, Cassidy-Bushrow AE, Kim H, Zoratti EM, Lukacs NW, Boushey HA, Ownby DR, Lynch SV, Johnson CC. Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Scientific reports 2016; 6: 31775.
  9. Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, Panzer AR, LaMere B, Rackaityte E, Lukacs NW, Wegienka G, Boushey HA, Ownby DR, Zoratti EM, Levin AM, Johnson CC, Lynch SV. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature medicine 2016; 22: 1187-1191.
  10. Fujimura KE, Demoor T, Rauch M, Faruqi AA, Jang S, Johnson CC, Boushey HA, Zoratti E, Ownby D, Lukacs NW, Lynch SV. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proceedings of the National Academy of Sciences of the United States of America 2014; 111: 805-810.
  11. Fonseca W, Lucey K, Jang S, Fujimura KE, Rasky A, Ting HA, Petersen J, Johnson CC, Boushey HA, Zoratti E, Ownby DR, Levine AM, Bobbit KR, Lynch SV, Lukacs NW. Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation. Mucosal immunology 2017; 10: 1569-1580.