The cross-kingdom interaction between Helicobacter pylori and Candida albicans

Abstract

Helicobacter pylori infection and transmission routesHelicobacter pylori is a gram-negative microaerophilic bacterium. The infection of H. pylori can increase the risk of gastric cancer which is the second leading cause of cancer death worldwide [1]. The World Health Organization's International Agency for Research on Cancer (IARC) has classified H. pylori as a type I (definite) carcinogen since 1994. H. pylori infection is a global health problem. In developed countries, its infection rate is 20% to 50%, while in developing countries, the infection rate of middle-aged people has reached 80% [2]. The fecaloral and the oral-oral routes are considered as the main transmission routes of H. pylori [3]. Nevertheless, only H. pylori genes have been detected in saliva and dental plaques, but culturable H. pylori has not been isolated yet in large quantities [4], indicating that there may be some new strategies of H. pylori to implement its transmission through oral cavity.Candida albicans, a dimorphic fungus, is one of the most common fungi in the human body [5]. It was noteworthy that C. albicans and H. pylori were abundant in certain human niches, such as the root canal necrotic pulp, stomach, duodenum, and vagina [6], suggesting that C. albicans may interact with H. pylori to promote the growth, spread, and infection of H. pylori in some nonadaptive condition, such as the oral cavity and vagina. The synergy between H. pylori and C. albicans in gastric diseasesH. pylori infection is positively correlated with yeast in gastric diseases [7]. A total of 36% gastric ulcers patients, 2% non-ulcerative dyspepsia patients, and 56% large-scale gastric ulcers (greater than 2 cm) patients with H. pylori have fungal co-colonization in the upper gastrointestinal tract, such as C. albicans and Candida krusei, indicating the strong relationship between fungi and H. pylori in ulcerative lesions [8]. C. albicans is highly correlated with H. pylori in gastric cancer, peptic ulcer, and chronic gastritis patients. The gastric ulcer patient with C. albicans and H. pylori in the stomach developed even larger ulcers. The presence of C. albicans was closely related to the prolongation of gastric diseases by the increase of healing time and persistence of clinical symptoms [9,10]. The strong positive correlation between C. albicans and H. pylori in the development of gastric diseases indicates their synergistic pathogenesis [7]. C. albicans may enhance the colonization, toxicity, and pathogenicity of H. pylori especially in gastrointestinal diseases through adhesion and the formation of a mixed species, like that C. albicans promotes the pathogenicity of other bacteria [11].

Helicobacter pylori, Protected from Antibiotics and Stresses Inside Candida albicans Vacuoles, Cause Gastritis in Mice

“…The endosymbiosis of H. pylori in yeast cells was indicated by the presence of H. pylori in Candida cytosols, referred to as “intravacuolar H. pylori ”, as previously mentioned [ 45 , 46 ]. As such, H. pylori and C. albicans were co-incubated under different conditions, including the bacteria– Candida ratio, pH of the media, and duration of incubation); the result was the identification of H. pylori inside Candida yeast cells, as illustrated by bacteria-like bodies (BLBs) (dense black dots in a state of movement) inside the yeast cells [ 40 , 41 , 43 , 47 , 48 , 49 , 50 ], using bright-field microscopy ( Figure 1 ).…”

“…H. Pylori can be established not only in eukaryotic human cells but also in eukaryotic microorganisms (e.g., Candida spp.) as a form of “prokaryotic–eukaryotic endosymbiosis” [ 41 , 45 , 47 ] in which the endosymbiotic bacteria are localized inside the membrane-bound vacuole [ 40 , 41 , 47 , 48 ]. Likewise, several examples of the endosymbiosis of endobacteria inside fungi have been described [ 51 ].…”

“…(intravacuolar H. pylori ), and it was proposed that yeast cells were a vehicle for transmitting H. pylori and protecting them from stressful environments [ 40 , 41 , 42 ]. Although the synergy of C. albicans with H. pylori (outside yeast cells) [ 43 ] and other bacteria [ 44 , 45 ] in enhancing the severity of inflammation via inter-kingdom co-operation is demonstrated partly through the promotion of bacterial colonization by Candida ’s epithelial adhesion property, data regarding the pathophysiology and clinical impacts of H. pylori inside Candida yeast cells are still very scarce. Here, we initiated intravacuolar H. pylori in vitro and tested the clinical impacts in vitro and in a mouse model.…”

The interactions between oral-gut axis microbiota and Helicobacter pylori

“…The main interaction patterns are coaggregation, symbiotic biofilm formation, endosymbiosis, etc. ( Nobbs and Jenkinson, 2015 ; Chen et al., 2021b ) ( Figure 1 ). Fusobacterium nucleatum and Porphyromonas gingivalis , key bacteria in periodontal diseases, can aggregate with H. pylori cells and the coaggregation was inhibited by EDTA, lysine, or arginine in vitro , indicating the potential promotion of H. pylori oral-to-stomach colonization by oral bacteria ( Okuda et al., 2003 ; Park et al., 2016 ).…”

“…Candida albicans is the most common fungus in the human body and its main habitats are the oral cavity, upper respiratory tract, and intestinal tract ( D'Enfert et al., 2020 ). C. albicans can synergize with H. pylori to enhance its survival in an unfavorable living environment and promote its colonization and the infection ( Chen et al., 2021b ). H. pylori was found to enter C. albicans yeast cells in the oral cavity and vagina, while the intracellular H. pylori showed active motility even under high temperature, dryness, and antibiotics conditions ( Saniee et al., 2013 ), indicating that the internalization synergistic relationship can protect H. pylori from unsuitable conditions.…”