AUTHOR=Bourgonje Arno R. , Roo-Brand Geesje , Lisotto Paola , Sadaghian Sadabad Mehdi , Reitsema Rosanne D. , de Goffau Marcus C. , Faber Klaas Nico , Dijkstra Gerard , Harmsen Hermie J. M. 

TITLE=Patients With Inflammatory Bowel Disease Show IgG Immune Responses Towards Specific Intestinal Bacterial Genera

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.842911

DOI=10.3389/fimmu.2022.842911

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Inflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD.</p></sec><sec><title>Methods</title><p>Fecal and serum samples were collected from patients with IBD (<italic>n</italic>=55) and age- and sex-matched healthy controls (<italic>n</italic>=55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing.</p></sec><sec><title>Results</title><p>IgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to <italic>Streptococcus</italic>, <italic>Lactobacillus</italic>, <italic>Lactococcus</italic>, <italic>Enterococcus</italic>, <italic>Veillonella</italic> and <italic>Enterobacteriaceae</italic>, as well as against specific <italic>Lachnospiraceae</italic> bacteria, including <italic>Coprococcus</italic> and <italic>Dorea</italic> (all <italic>P</italic>&lt;0.001), and to <italic>Ruminococcus gnavus</italic>-like bacteria (<italic>P</italic>&lt;0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the <italic>Lachnospiraceae</italic> members <italic>Roseburia</italic> and <italic>Blautia</italic>, to <italic>Faecalibacterium</italic>, as well as to <italic>Bacteroides</italic>. Patients with IBD showed more IgG-coating of <italic>Streptococcus</italic>, <italic>Lactobacillus</italic>, and <italic>Lactococcus</italic> bacteria compared to healthy controls (all <italic>P</italic>&lt;0.05). No differences in IgG-coated bacterial fractions were observed between Crohn’s disease and ulcerative colitis, between active or non-active disease, nor between different disease locations.</p></sec><sec><title>Conclusion</title><p>The IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria.</p></sec>