Other Gastric and Enterohepatic Helicobacter Species


Since the discovery of Helicobacter pylori and the demonstration of its causal relationship with human gastroduodenal disease, investigators have identified numerous non− Helicobacter pylori Helicobacter (NHPH) species. These other Helicobacter spp. are frequently found in domestic and wild animals and have been recovered from the stomach, intestine, and hepatobiliary systems of humans. Although the complete spectrum of human disease syndromes associated with NHPH remains to be fully defined, gastric and enterohepatic diseases have been described.

The Pathogens

There are now >30 formally named species in the genus Helicobacter . In addition, there are provisional species that have been named but not yet validated. NHPH are spiral-shaped bacilli that are gram-negative, motile, and microaerophilic. They are broadly grouped as gastric or enterohepatic, based on their biologic niche ( Table 175.1 ).

TABLE 175.1
Gastric and Enterohepatic Helicobacter Species Identified in Humans
Species Location
H. bizzozeronii Gastric
H. felis Gastric
H. heilmannii Gastric
H. pylori Gastric
H. salomonis Gastric
H. suis Gastric
H. bilis Enterohepatic
H. canadensis Enterohepatic
H. canis Enterohepatic
H. cinaedi Enterohepatic
H. fennelliae Enterohepatic
H. ganmani Enterohepatic
H. hepaticus Enterohepatic
H. pullorum Enterohepatic

The gastric NHPH spp. are urease- and catalase-positive. They can be distinguished from H. pylori by their longer, more tightly coiled morphology and their difficulty to culture in vitro ( Fig. 175.1 ). Microscopically, the gastric NHPH spp. are very similar to one another, although differences in size, the presence or absence of periplasmic fibers, and number and distribution of flagella have been described. , The first gastric NHPH to be discovered was an uncultivated organism, initially called Gastrospirillum hominis , and later Helicobacter heilmannii . , Subsequently, several additional gastric Helicobacter spp. were identified, including H. felis , H. suis , H. bizzozeronii , and H. salomonis . The gastric NHPH spp. have been associated with gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma in humans.

FIGURE 175.1, Morphologic differences between H. pylori and H. heilmannii s.l. The longer, more tightly-coiled H. heilmannii s.l. (A) can be distinguished from H. pylori (B) in gastric tissue. Helicobacter spp. can be viewed with hematoxylin and eosin stain, Giemsa stain (A), or silver stain (B). (Photo courtesy of Dr. Milton J. Finegold.)

The nomenclature of the gastric NHPH has produced confusion, largely owing to challenges in culturing the various organisms. Historically, long, spiral-shaped, uncultivable organisms in the human stomach were called H. heilmannii . However, the sequencing of specific target genes demonstrated that a group of Helicobacter spp. was actually present. Haesbrouck and colleagues proposed that H. heilmannii sensu lato ( H. heilmannii s.l.) refer to the whole group of gastric NHPH spp. when only histopathologic or electron microscopic data are available and to reserve the use of species names when definitive identification at the species level is available. The term H. heilmannii sensu stricto ( H. heilmannii s.s.) refers to the particular H. heilmannii species. The complete genome for 4 of the 5 gastric NHPH spp. (i.e., H. suis , H. felis , H. bizzozeronii , and H. heilmannii s.s.) has been published. The genomes reveal that these organisms, while possessing homologs to H. pylori genes associated with colonization, lack homologs to important H. pylori virulence genes, including the cag pathogenicity island and the genes encoding CagA and VacA. An exception is H. suis , which contains a VacA homolog. These genetic differences may explain the pathologic differences that have been observed between the gastric NHPH and H. pylori .

The enterohepatic Helicobacter spp. are fastidious organisms found in the intestines, liver, and biliary tract of humans, other mammals, and birds. They have ultrastructural and physiologic features in common with gastric Helicobacter spp.; however, they generally do not colonize the gastric mucosa. Several enterohepatic NHPH spp. have been found in humans, including H. bilis , H. canis , H. cinaedi , H. fennelliae , H. pullorum , and H. hepaticus ( Table 175.1 ). The enterohepatic NHPH spp. have been associated with gastroenteritis, hepatitis, benign biliary disease, and hepatobiliary malignancies. H. cinaedi has been reported to cause bacteremia, cellulitis, and arthritis. Recent interest in the enterohepatic NHPH has resulted in the sequencing of the entire genome for several species, including H. cinaedi , H. bilis , H. canis , H. hepaticus , and H. pullorum .

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