Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares.
Ann Rheum Dis
; 82(10): 1315-1327, 2023 10.
Article
in En
| MEDLINE
| ID: mdl-37365013
ABSTRACT
OBJECTIVE:
Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities.METHODS:
In an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed.RESULTS:
Multivariate analyses documented that, unlike healthy controls, significant temporal community-wide ecological microbiota instability was common in SLE patients, and transient intestinal growth spikes of several pathogenic species were documented. Expansions of only the anaerobic commensal, Ruminococcus (blautia) gnavus (RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares.CONCLUSIONS:
Our findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lupus Nephritis
/
Microbiota
/
Gastrointestinal Microbiome
/
Lupus Erythematosus, Systemic
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Ann Rheum Dis
Year:
2023
Type:
Article
Affiliation country:
United States