# Nutrient Deficiency Promotes the Entry of _Helicobacter pylori_ Cells into _Candida_ Yeast Cells
## 1 Introduction  
_Helicobacter pylori_ is a bacterial pathogen which infects the gastric epithelium of more than 50% of the world population. The infection caused by this bacterium may produce gastric and extra-gastric pathologies [1; 2]. Gastric pathologies include an acute/chronic gastritis present in 100% of the infected population which, when not treated, may progress to more severe conditions, including atrophic gastritis, intestinal metaplasia and, even more severe, gastric cancer [3; 4; 5]. Since 1994, _H. pylori_ has been considered to be a type I carcinogen for humans by the Agency for Research on Cancer [6]. Gastric cancer is the fifth most common cancer in humans and third in cancer-caused deaths worldwide [4]. Although not all _H. pylori_ infected persons will develop this type of cancer, the literature reports the close relationship between the infection with _H. pylori_ and the progression to gastric cancer [4]. Therefore, the Maastricht V Consensus established that all persons positive for _H. pylori_ require antibiotic treatment [7]. Among the extra-gastric pathologies caused by _H. pylori_, it is possible to mention, among others, idiopathic thrombocytopenia pur pur purura and iron deficiency anemia [8; 9]. The conditions provided by the gastric environment where _H. pylori_ survives are challenging to replicate in the laboratory, making this pathogen a fastidious microorganism to culture in vitro [10; 11; 12]. Enriched culture media, such as Brucella agar or broth, Columbia agar (CA), brain heart infusion agar, or trypticase soy agar, provide the nutritional requirements for bacterial isolation. Due to its role as an enzymatic cofactor and its role in electron transport, iron is an essential element for the metabolism of organisms [13; 14]. Therefore, all culture media to culture _H. pylori_ must be supplemented with an iron source such as 5% to 10% horse blood or serum. Fetal bovine serum (FBS) can be used as an alternative (at the same concentrations), and Brucella broth can be supplemented with either 5% to 10% FBS or equine serum [15]. In both cases, supplementation with blood or serum provides the same function, serving as an iron source for _H. pylori_[12; 15; 16]. Despite the nutritional and environmental demands required by _H. pylori_, this bacterium can be detected using molecular techniques in the oral cavity, amplifying specific genes of this microorganism in dental plaque, saliva, dental pulp, and in 30% of cases of severe cavities in children between 4 and 7 years [17; 18; 19]. Furthermore, the genes of _H. pylori_ have been amplified by PCR from environmental sources such as tap water, insects (e.g., flies and blowflies), raw sheep meat, feces and raw milk from cows, buffaloes and sheep [20; 21; 22; 23]. The diversity of environmental sources from where _H. pylori_ genes have been amplified and the difficulty of isolating this bacterium from those sources raise the following questions: how does _H. pylori_ DNA reach extra gastric locations? Is the survival of this bacterium possible in extra-gastric niches? It has been reported that _H. pylori_ in extra-gastric environments is capable of varying its morphology from helical to coccoid (viable non-culturable stage) [24; 25]. It has also been observed that under specific environmental stimuli such as cold stress, pH, aerobiosis, and aging, its metabolism of ATP, polyphosphate and RNA can vary, and its urease activity decreases [18; 19]. Under FBS starvation, the bacterium, in addition to decreasing its metabolism, is capable of forming biofilms to ensure its survival [25; 26]. However, if the stress conditions are not reversed in time, bacterial death will occur, and therefore, the question of how _H. pylori_ survives in extra-gastric niches remains unanswered. In this sense, further investigation could unravel the intracellular association between _H. pylori_ and yeast cells.