SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Oct. 6, 2020, is named 56708-740_301_SL and is 7,414 bytes in size.

TECHNICAL FIELD

This invention is in the field of compositions comprising bacterial strains isolated from the mammalian digestive tract and the use of such compositions in the treatment of disease, in particular in stimulating the immune system in the treatment of disease.

BACKGROUND TO THE INVENTION

The human intestine is thought to be sterile in utero, but it is exposed to a large variety of maternal and environmental microbes immediately after birth. Thereafter, a dynamic period of microbial colonization and succession occurs, which is influenced by factors such as delivery mode, environment, diet and host genotype, all of which impact upon the composition of the gut microbiota, particularly during early life. Subsequently, the microbiota stabilizes and becomes adult-like [1]. The human gut microbiota contains more than 500-1000 different phylotypes belonging essentially to two major bacterial divisions, the Bacteroidetes and the Finnicutes [2]. The successful symbiotic relationships arising from bacterial colonization of the human gut have yielded a wide variety of metabolic, structural, protective and other beneficial functions. The enhanced metabolic activities of the colonized gut ensure that otherwise indigestible dietary components are degraded with release of by-products providing an important nutrient source for the host. Similarly, the immunological importance of the gut microbiota is well-recognized and is exemplified in germfree animals which have an impaired immune system that is functionally reconstituted following the introduction of commensal bacteria [3-4].

Dramatic changes in microbiota composition have been documented in gastrointestinal disorders such as inflammatory bowel disease (IBD). For example, the levels ofClostridiumcluster XIVa bacteria are reduced in IBD patients whilst numbers ofE. coliare increased, suggesting a shift in the balance of symbionts and pathobionts within the gut [5-6]. Interestingly, this microbial dysbiosis is also associated with imbalances in T effector cell populations.

In recognition of the potential positive effect that certain bacterial strains may have on the animal gut, various strains have been proposed for use in the treatment of various diseases (see, for example, [7-8]). Also, certain strains, including mostlyLactobacillusandBifidobacteriumstrains, have been proposed for use in treating various inflammatory and autoimmune diseases that are not directly linked to the intestines (see [9] and [10] for reviews). CertainStreptococcusandVeillonellastrains, and to a lesser extent,EnterococcusandLactobaccillusstrains have been suggested to have immunomodulatory effects, with varying effects on different cytokines in vitro, suggesting that data obtained in vitro with individual strains are unlikely to adequately represent immune responses to mixtures of gut microbiota communities in vivo [88]. However, the relationship between different diseases and different bacterial strains, and the precise effects of particular bacterial strains on the gut and at a systemic level and on any particular types of diseases, are poorly characterised.

There is a requirement in the art for new methods of treating diseases. There is also a requirement for the potential effects of gut bacteria to be characterised so that new therapies using gut bacteria can be developed.

SUMMARY OF THE INVENTION

The inventors have developed new compositions comprising a bacterial strain of the speciesEnterococcus gallinarumthat can be used in stimulating the immune system and treating and preventing disease. The inventors have identified that strains of the speciesEnterococcus gallinarumcan potently activate the immune system and can treat cancer, which indicates that they may able to also treat other diseases where activation of the immune system may be useful.

The invention therefore provides a composition comprising a bacterial strain of the speciesEnterococcus gallinarum, for use in stimulating the immune system in subject.

In further aspects, the invention provides a composition comprising a bacterial strain of the speciesEnterococcus gallinarum, for use in treating, preventing or delaying immunosenescence.

In further aspects, the invention provides a composition comprising a bacterial strain of the speciesEnterococcus gallinarum, for use as a vaccine adjuvant.

In further aspects, the invention provides a composition comprising a bacterial strain of the speciesEnterococcus gallinarum, for use in enhancing a cell therapy, such as CAR-T.

Preferably, the bacteria used in the invention is the strain deposited under accession number 42488 at NCIMB.

In further preferred embodiments, the bacteria used in the invention is the strain deposited under accession number 42761 at NCIMB.

