In 1979, Marshall was appointed Registrar in Medicine at the
Royal Perth Hospital. He met Dr.
Robin Warren, a pathologist interested in
gastritis, during internal medicine fellowship training at Royal Perth Hospital in 1981. Together, they both studied the presence of spiral bacteria in association with gastritis. In 1982, they performed the initial culture of
H. pylori and developed their hypothesis on the bacterial cause of peptic ulcers and gastric cancer. On the other hand, it has also been argued that medical researchers showed a proper degree of
scientific scepticism until the
H. pylori hypothesis could be supported by evidence. In 1982, Marshall and Warren obtained funding for one year of research. The first 30 out of 100 samples showed no support for their hypothesis. However, it was discovered that the lab technicians had been throwing out the cultures after two days. This was standard practice for throat swabs where other organisms in the mouth rendered cultures unusable after two days. Due to other hospital work, the lab technicians did not have time to immediately throw out the 31st test on the second day, and so it stayed from Thursday through to the following Monday. In that sample, they discovered the presence of
H. pylori. They later found out that
H. pylori grows more slowly than the conventional two days required by other mucosal bacteria, and that stomach cultures were not contaminated by other organisms. In 1983, they submitted their findings thus far to the Gastroenterological Society of Australia, but the reviewers turned their paper down, rating it in the bottom 10% of those they received that year. He was surprised when, only three days later, he developed vague nausea and
halitosis, due to the
achlorhydria. There was no acid to kill bacteria in the stomach and their waste products manifested as
bad breath, noticed by his wife. On days 5–8, he developed achlorhydric (no acid) vomiting. On day eight, he had a repeat endoscopy, which showed massive inflammation (gastritis), and a
biopsy from which
H. pylori was cultured, showing it had colonised his stomach. On the fourteenth day after ingestion, a third endoscopy was done, and Marshall began to take antibiotics. Marshall did not develop antibodies to
H. pylori, suggesting that
innate immunity can sometimes eradicate acute
H. pylori infection. Marshall's illness and recovery, based on a culture of organisms extracted from a patient, fulfilled
Koch's postulates for
H. pylori and gastritis, but not for peptic ulcers. This experiment was published in 1985 in the
Medical Journal of Australia and is among the most cited articles from the journal. After his work at
Fremantle Hospital, Marshall did research at Royal Perth Hospital (1985–86) and at the
University of Virginia, USA (1986–present), before returning to Australia while remaining on the faculty of the University of Virginia. Marshall continues research related to
H. pylori and runs the
H. pylori Research Laboratory at UWA. In 2007, Marshall was appointed Co-Director of The Marshall Centre for Infectious Diseases Research and Training, founded in his honour. In addition to
Helicobacter pylori research, the Centre conducted varied research into infectious disease identification and surveillance, diagnostics and drug design, and transformative discovery. His research group expanded to embrace new technologies, including
Next-Generation Sequencing and
genomic analysis. Marshall also accepted a part-time appointment at the
Pennsylvania State University that same year. He established the Noisy Guts Project in 2017 – a research team dedicated to investigating new diagnostics and treatments for
irritable bowel syndrome. This resulted in a spin-out company, Noisy Guts Pty Ltd, which develops
functional food products. In August 2020, Marshall, along with Simon J. Thorpe, accepted a position at the scientific advisory board of
Brainchip INC, a computer chip company. ==Awards and honours==