Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation.

BACKGROUND & AIMS: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE). METHODS: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing. Functional outcomes of microbiota colonization were assessed by RNA sequencing analysis of mouse esophageal epithelium and compared with the human EoE transcriptome. The impact of dysbiosis was assessed using a preclinical model of EoE. RESULTS: We found that the murine esophagus is colonized with diverse microbial communities within the first month of life. The esophageal microbiota is distinct, dominated by Lactobacillales, and demonstrates spatial heterogeneity as the proximal and distal esophagus are enriched in Bifidobacteriales and Lactobacillales, respectively. Fecal matter transplantation restores the esophageal microbiota, demonstrating that the local environment drives diversity. Microbiota colonization modifies esophageal tissue morphology and gene expression that is enriched in pathways associated with epithelial barrier function and overlapping with genes involved in EoE, including POSTN, KLK5, and HIF1A. Finally, neonatal antibiotic treatment reduces the abundance of Lactobacillales and exaggerates type 2 inflammation in the esophagus. Clinical data substantiated loss of esophageal Lactobacillales in EoE compared with controls. CONCLUSIONS: The esophagus has a unique microbiome with notable differences between its proximal and distal regions. Fecal matter transplantation restores the esophageal microbiome. Antibiotic-induced dysbiosis exacerbates disease in a murine model of EoE. Collectively, these data establish the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interaction in the esophagus and have implications for gastrointestinal health and disease.

Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women.

The female genital tract (FGT) is an important site of human immunodeficiency virus (HIV) infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg), natural killer (NK) cells, CXCR5+ CD8+ T cells, T follicular helper (Tfh) cells, and T regulatory cells (Tregs) in the vaginal mucosa as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5+ CD8+ T cells, and Tfh cells in HESN females compared to HIV-unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp. in the mucosa. The findings suggest that the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators, and critical T cell subsets that protect against HIV infection. IMPORTANCE The vast majority of human immunodeficiency virus (HIV) infections across the world occur via the sexual route. The genital tract mucosa is thus the primary site of HIV replication, and discerning the nature of HIV-specific immune responses in this compartment is crucial. The role of the innate immune system at the mucosal level in exposed seronegative individuals and other HIV controllers remains largely unexplored. This understanding can provide valuable insights to improve vaccine design. We investigated mucosal T follicular helper (Tfh) cells, CXCR5+ CD8+ T cells, natural killer (NK) cells subsets, soluble immune markers, and microbiome diversity in HIV-exposed seronegative (HESN) women. We found a significantly higher level of mucosal CXCR5+ CD8+ T cells, CD4+ Tfh cells, activated NK cell subsets, and antiviral immune cell mediators in HESN women. We also found a higher abundance of Gardnerella spp., microbiome dysbiosis, and decreased levels of inflammatory markers to be associated with reduced susceptibility to HIV infection. Our findings indicate that increased distribution of mucosal NK cells, CXCR5+ CD8+ T cells, Tfh cells, and soluble markers in HIV controllers with a highly diverse cervicovaginal microbiome could contribute effectively to protection against HIV infection. Overall, our findings imply that future vaccine design should emphasize inducing these highly functional cell types at the mucosal sites.

Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review.

Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent-not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.

The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms.

Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms.

Treatment of non-erosive reflux disease and dynamics of the esophageal microbiome: a prospective multicenter study.

Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.

Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.

INTRODUCTION: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett's microbiota could link to risk factors, providing risk of progression to neoplasia. METHODS: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria and analyzed by 16S ribosomal ribonucleic acid V4 gene DNA sequencing. Taxa composition was tested using a generalized linear model based on the negative binomial distribution and the log link functions of the R Bioconductor package edgeR. RESULTS: The microbe composition of paired samples (disease vs nondisease) comparing normal esophagus with intestinal metaplasia, low grade dysplasia, high grade dysplasia, and adenocarcinoma showed significant decreases in the phylum Planctomycetes and the archaean phylum Crenarchaeota (P < 0.05, false discovery rate corrected) in diseased tissue compared with healthy controls and intrasample controls (gastric juice and unaffected mucosa). Genera Siphonobacter, Balneola, Nitrosopumilus, and Planctomyces were significantly decreased (P < 0.05, false discovery rate corrected), representing <10% of the entire genus community. These changes were unaffected by age, tobacco use, or sex for Crenarcha. DISCUSSSION: There are similar significant changes in bacterial genera in Barrett's esophageal mucosa, dysplasia, and adenocarcinoma compared with controls and intrapatient unaffected esophagus. Further work will establish the biologic plausibility of these specific microbes' contributions to protection from or induction of esophageal epithelial dysplasia.

Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial.

INTRODUCTION: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression. METHODS: In this randomized controlled trial, patients scheduled to undergo endoscopy for clinical indications used chlorhexidine mouth rinse or no treatment for 2 weeks before endoscopy. Oral swabs and saliva were collected at baseline and at follow-up, and the esophagus was sampled on the day of endoscopy. The microbiome was analyzed by 16S rRNA gene sequencing, and esophageal tissue gene expression was ascertained by RNA-Seq. RESULTS: Twenty subjects were enrolled and included in the analyses. Within individuals, the oral and esophageal microbiome composition was significantly correlated. Chlorhexidine treatment associated with significant alterations to the relative abundance of several esophageal bacterial taxa, and to expression of genes in the esophagus including reductions in periostin, claudin-18, chemokines CXCL1 and CXCL13, and several members of the tumor necrosis factor receptor superfamily. A taxon in genus Haemophilus in the esophagus also associated with significant changes in tissue gene expression. DISCUSSION: The oral and esophageal microbiomes are closely related within individuals, and esophageal microbiome alterations correlate with tissue gene expression changes. The esophageal microbiome may act as an important cofactor that influences pathogenesis and outcomes of diseases such as eosinophilic esophagitis, gastroesophageal reflux, and Barrett's esophagus.

Calcium-sensing receptor deletion in the mouse esophagus alters barrier function.

Calcium-sensing receptor (CaSR) is the molecular sensor by which cells respond to small changes in extracellular Ca2+ concentrations. CaSR has been reported to play a role in glandular and fluid secretion in the gastrointestinal tract and to regulate differentiation and proliferation of skin keratinocytes. CaSR is present in the esophageal epithelium, but its role in this tissue has not been defined. We deleted CaSR in the mouse esophagus by generating keratin 5 CreER;CaSRFlox+/+compound mutants, in which loxP sites flank exon 7 of CaSR gene. Recombination was initiated with multiple tamoxifen injections, and we demonstrated exon 7 deletion by PCR analysis of genomic DNA. Quantitative real-time PCR and Western blot analyses showed a significant reduction in CaSR mRNA and protein expression in the knockout mice (EsoCaSR-/-) as compared with control mice. Microscopic examination of EsoCaSR-/- esophageal tissues showed morphological changes including elongation of the rete pegs, abnormal keratinization and stratification, and bacterial buildup on the luminal epithelial surface. Western analysis revealed a significant reduction in levels of adherens junction proteins E-cadherin and ß catenin and tight junction protein claudin-1, 4, and 5. Levels of small GTPase proteins Rac/Cdc42, involved in actin remodeling, were also reduced. Ussing chamber experiments showed a significantly lower transepithelial resistance in knockout (KO) tissues. In addition, luminal-to-serosal-fluorescein dextran (4 kDa) flux was higher in KO tissues. Our data indicate that CaSR plays a role in regulating keratinization and cell-cell junctional complexes and is therefore important for the maintenance of the barrier function of the esophagus.NEW & NOTEWORTHY The esophageal stratified squamous epithelium maintains its integrity by continuous proliferation and differentiation of the basal cells. Here, we demonstrate that deletion of the calcium-sensing receptor, a G protein-coupled receptor, from the basal cells disrupts the structure and barrier properties of the epithelium.

Real-time PCR detection of a 16S rRNA single mutation of Helicobacter pylori isolates associated with reduced susceptibility and resistance to tetracycline in the gastroesophageal mucosa of individual hosts.

The molecular mechanism of Helicobacter pylori resistance to tetracycline involves mutations in the primary binding site of the ribosome. A resistance or reduced susceptibility to tetracycline could be the result of single, double or triple mutations in the 16S rRNA gene of H. pylori. We investigated if the genotype was correlated to tetracycline resistance as determined phenotypically in vitro for 96 H. pylori isolates in the gastroesophageal mucosa of Venezuelan individual hosts. E-test for antimicrobial susceptibility test and real-time PCR for the detection of 16S rRNA gene mutations were performed in 96 H. pylori isolates (48 obtained from antrum, and 48 from oesophagus) from eight dyspeptic patients. In the gastric mucosa, 38 isolates were identified sensitive and 10 resistant to tetracycline by E-test, whereas 44 sensitive and 4 resistant isolates were found in the oesophagus. Real-time PCR detection of the 16S rRNA gene exhibited mutants with a single base-pair substitution (AGA926GGA) in six antrum isolates and seven oesophagus isolates, whereas only three harboured a low level of tetracycline resistance in vitro. Our results indicate that real-time PCR detection of 16S rRNA is a reliable method to classify among tetracycline-resistant genotypes and useful in patients who have experienced a first-line treatment failure with triple therapy.

Microbiota of the Oropharynx and Endoscope Compared to the Esophagus.

The role of the microflora in the development of esophageal disease is still largely unknown and is being investigated in more detail. Our goal was to determine how the microbiota levels of endoscope and uvular swabs compared to the levels of tissue biopsies along various points of the esophagus. 17 patients with Barrett's esophagus agreed to participate in the study. Biopsies of esophageal mucosa were taken from the (1) proximal esophagus, (2) mid-esophagus, (3) distal esophagus, and (4) Barrett's esophagus. Swabs were also taken from the uvula and the endoscope. Throughout the esophagus, 17 bacterial genera were detected from the samples. The microflora pattern obtained from the uvula and endoscopic swabs did not correlate well with mucosal biopsies along any aspect of the esophagus. There were statistically significant differences in the levels and proportions of bacteria found when comparing the uvula swab to the esophageal biopsies and when comparing the endoscope swab to the esophageal biopsies. Obtaining a simple swab of the uvula or endoscope itself appears to be a poor substitute for tissue biopsy of esophageal mucosa when evaluating microflora patterns. When performing microflora studies of the esophagus, mucosal biopsies should be used for analysis.

Arginase-1 and Treg Profile Appear to Modulate Inflammatory Process in Patients with Chronic Gastritis: IL-33 May Be the Alarm Cytokine in H. pylori-Positive Patients.

Helicobacter pylori (H. pylori) is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing H. pylori infection. This study is aimed at analyzing the mRNA expression of the cytokines IFN-γ, IL-17, IL-10, TGF-ß, IL-6, IL-22, IL-23, and IL-33; transcription factors T-bet, RORC, and FOXP3; enzymes ARG1, ARG2, and NOS2; and neuropeptides VIP and TAC and their respective receptors VIPR1 and TACR1 in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the ARG1 gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the TGF-ß gene and its FOXP3 transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of IFN-γ, IL-17, IL-10, and TGF-ß and the transcription factors, T-bet and RORC, in the presence or absence of H. pylori showed no significant difference. However, the expression of FOXP3 was significantly lower in H. pylori-positive patients than that in H. pylori-negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that IL-33 may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori (H. pylori) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

Esophageal Mycobacterium avium-intracellulare infection in a bone marrow transplant patient: Case report and literature review.

Mycobacterium avium-intracellulare complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) disease in humans. We report a case of esophageal MAC disease in a patient who had allogeneic bone marrow transplant for acute lymphoblastic leukemia. Although pulmonary MAC in immunocompromised host is not uncommon, there are only a few cases of NTM-associated esophageal mass reported. Our report and literature review highlight the importance of considering MAC in the differential diagnosis of dysphagia or odynophagia.

Point Mutations at gyrA and gyrB Genes of Levofloxacin-Resistant Helicobacter pylori Isolates in the Esophageal Mucosa from a Venezuelan Population.

The treatment of Helicobacter pylori infection is complicated by antibiotic resistance. A high levofloxacin (LVX) resistance rate was previously demonstrated in H. pylori isolates from gastric mucosa (40%) and esophagus (19%) in individual hosts of a Venezuelan population. We aimed to assess the molecular mechanisms of LVX resistance and susceptibility in isolates from the gastroesophageal mucosa, by studying point mutations in the quinolone resistance-determining region of gyrA and gyrB genes. Sequencing of gyrA and gyrB genes (N = 120) helped to identify point mutations in 60 isolates (30 from antrum and 30 from esophagus) of five dyspeptic patients. Double (Asn87Thr and Asp91Asn) and single (Asn87Ile or Asn87Thr) mutations in the gyrA gene were identified in the esophageal mucosa. These mutations have been commonly found in the stomach. Occurrence of a single (Asn87Ile) mutation was associated with high resistance (minimum inhibitory concentration ≥ 32 µg/mL) to LVX. Only a single (Ser479Gly) mutation was found in the gyrB gene in both mucosae. One patient presented isolates with no mutations in the two genes studied. Isolates with the same mutation pattern in individual hosts revealed identical genetic profiles for these genes, confirming that isolates identified in the esophageal mucosa come from isolates colonizing the stomach. Helicobacter pylori resistance to LVX in the esophagus is related to double- and single-point mutations in gyrA and gyrB genes, such as those found in the stomach. Levofloxacin should be applied with caution, because its antibiotic effect on H. pylori is decreasing in Latin America, perhaps owing to high prescription rates.

Increased Variance in Oral and Gastric Microbiome Correlates With Esophagectomy Anastomotic Leak.

BACKGROUND: Anastomotic leak after esophagectomy remains a significant source of morbidity and mortality. The gastrointestinal (GI) microbiome has been found to play a significant role in tumor oncogenesis and postoperative bowel anastomotic leak. We hypothesized that the GI microbiome could differentiate between esophageal cancer histologies and predict postoperative anastomotic leak. METHODS: A prospective study of esophagectomy patients was performed from May 2013 to August 2014, with the collection of oral saliva, intraoperative esophageal and gastric mucosa, and samples of postoperative infections (neck swab or sputum). The presence and level for each bacterial probe as end points were used to analyze correlations with tumor histology, tumor stage, and presence of postoperative complications by unequal variances t tests for multiple comparisons and principal coordinate analysis. RESULTS: Esophagectomy was successful in 55 of 66 patients who were enrolled. Among those, the diagnosis was adenocarcinoma in 44 (80%) squamous cell carcinoma in (13%), and benign disease in 4 (7%). The 30-day mortality was 1.8% (1 of 55). Complications included anastomotic leak requiring local drainage in 18% (10 of 55) and postoperative pneumonia in 2% (1 of 55). No correlation was noted between GI microbiome flora and tumor histology or tumor stage. A significant difference (p = 0.015) was found when the variance in bacterial composition between the preoperative oral flora was compared with intraoperative gastric flora in patients who had a leak but not in patients with pneumonia. CONCLUSIONS: Patients with anastomotic leaks had increased variance in their preoperative oral and gastric flora. Microbiome analysis could help identify patients at higher risk for leak after esophagectomy.

PHYSIOLOGY OF SYMBIOTIC AND OWN MAN DIGESTION.

Aimlo observe the qualitative and quantitative composition of the luminal and mucosal microflora in the functional departments of digestive tract, determine its participation in the fermentation of food ingredients and place of symbiotic digestion in the digestive conveyor. MATERIALS AND METHODS: The study involved 107 healthy volunteers aged 18-36 years. The qualitative and quantitative composition, enzymatic activity of the oral fluid on the surface of the cheeks and tongue, and the contents of the biopsies of the esophagus, stomach, duodenum,jejunum, ileum and colon have been studied. RESULTS: Symbiotic digestion is carried out by luminal and mucosal microflora provided cavitary and parietal bacterial dilestion in all parts of the digestive tract. Symbiotic digestion included in the own digestion takes place in the fermentation of food ingredients, complementing and extending the assimilation processes. gondusion. The obtained data allowed to expand understanding of the digestive, process in humans, the first describe four phases of enteric digestion, propose a scheme of digestive convey or that includes mechanisms of the own and symbiotic digestion in all its departments.