Microniches within the gastric glands of the stomach house a reservoir of Helicobacter pylori, according to new research in mice. The findings indicate a potential strategy by which H. pylori bacteria colonize and persist in the stomach.

3D confocal image of mouse stomach infected with H. pylori showing microcolonies in the gastric glands. Image courtesy of M. R. Amieva, Stanford University, USA.

Mice were infected with H. pylori PMSS1 strains that expressed different coloured fluorescent proteins to track the dynamics of mixed or sequential chronic infections in the stomach. These bacterial populations were visualized in the intact stomach using 3D confocal microscopy in combination with the passive CLARITY technique, which renders tissue optically transparent. “These high-resolution imaging methods allowed us to map the location of H. pylori through an entire organ with unprecedented spatial resolution,” explains author Manuel Amieva.

The researchers observed that a small number of bacteria establish colonies deep in the gastric glands, with these populations able to expand in size and colonize adjacent glands over time, persisting throughout chronic infection. Notably, gland-associated populations did not mix with free-swimming bacteria in the surface mucus and excluded competitors from this microniche.

Host factors that regulate H. pylori gland colonization were also examined. Both the age at infection (mice infected as neonates had higher numbers of bacteria per gland than mice infected as adults) and host T cell responses affected the density of these gland-associated bacteria during chronic infection.

a potential strategy by which H. pylori bacteria colonize and persist in the stomach

“Our results led us to propose that microniches in the gastric glands provide a protected niche for H. pylori to maintain a stable reservoir that can replenish the more transient populations in the superficial mucosa,” says Amieva. “Given that the gland-associated populations induce inflammation and hyperplasia of the gastric tissue and are critical for persistence and competition, understanding how H. pylori establishes and maintains this chronic reservoir in the glands will improve H. pylori clearance strategies to prevent pathology and disease,” he concludes.