The current disclosure provides microorganisms, such as
lactic acid bacteria (e.g.,
Lactococcus lactis) containing an exogenous
nucleic acid encoding an IL-10 polypeptide and an exogenous
nucleic acid encoding a T1D-specific
antigen (e.g., a
proinsulin) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial
chromosome. Such microbial strains are suitable for human therapy. The disclosure further provides compositions (e.g., pharmaceutical compositions) methods of using the microorganisms and compositions, e.g., for the treatment of type 1 diabetes (T1D), including those with residual beta-
cell function, e.g., recent-onset T1D. The
microorganism may be administered orally, delivers the
microorganism into the
gastrointestinal tract, where it is released and expresses the bioactive polypeptides. The methods of the present disclosure are particularly well suited for subjects possessing residual beta-
cell function, e.g., for subjects with recent-onset T1D.