Factors affecting the composition of the upper gastrointestinal microbiota

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

The gastroesophageal microbiota is shaped by the oral cavity, pharynx and stomach due to the migration of oral bacteria to the esophagus and the reflux of the microflora in the stomach. Noticeably, this varies considerably from person to person, even among seemingly healthy people.

In addition to anatomic location, factors that have been reported to alter esophageal microbiota composition include age, diet, use of proton pump inhibitors (PPIs), oral hygiene and smoke. Studies of these factors have helped provide a framework for understanding the gastrointestinal microbiota.

Age:
Age has an effect on the gastrointestinal microbiota, although the full significance is yet to be determined.
With aging, humans appear to have a less dramatic, but still noticeable, change in the gastrointestinal microbiota. Esophageal microbiological assessment of adults aged 30 to 60 years, using 16S rRNA-, 18S rRNA-amplicon sequencing and shotgun sequencing, found age to be an important factor promoting promote microbial composition. Notably, they showed a positive correlation with age and the relative abundance of bacteria such as some Streptococcus spp., including Streptococcus parasanguinis, with increasing age. Furthermore, the increase in age was negatively correlated with the prevalence of Bacteroidetes including Prevotella melaninogenica.
Diet:
Dietary factors affecting the colon microbiota in childhood (breastfeeding versus formula) and in adulthood (affecting colon microbiota) with short-term macronutrient changes).
During early life, breastfeeding, formula feeding, and solid food feeding play a large role in the development of the gastrointestinal microbiota.
In adults, the gastroesophageal microbiota and its relationship to diet are still under investigation. Our focus here will be on diet and its relationship with esophageal disease to serve as a basis for possible future studies on the role of the microbiome in the gastroesophageal junction. . One study specifically looking at the relationship of diet to the gastrointestinal microbiota evaluated patients with high overall fiber versus high fat intake and found that dietary fiber but not dietary fat is associated with distinct esophageal microbiota.

PPI:
PPIs are first-line therapy for many esophageal disorders such as reflux esophagitis, erosive esophagitis, and Barrett's esophagus. The use of PPIs has been shown to alter both gastroesophageal and colon microbiota, although the full extent is unknown. The most clearly defined role is to reduce gastric acidity, thereby allowing the persistence of oral organisms that populate the distal esophagus. This pH-related microbiome alteration could allow the breeding of bacterial species that would not otherwise grow under more acidic conditions. For example, a significant increase in oral microorganisms such as Rothia dentocariosa, Rothia mucilaginosa, Scardovia spp. , and Actinomyces spp. in the gut microbiota has been reported following PPI administration.
Oral Hygiene:
Oral hygiene is thought to play an important role in the gastrointestinal microbiota. Bacteria found in the oral cavity can travel from afar through the defatting process. The role of the oral microbiota in colonizing the esophagus and becoming part of the general gastroesophageal microbiome, remains uncertain.
Oral hygiene is associated with a higher prevalence of gram-positive cocci and rods, mainly including Streptococcus spp. , in contrast to those with poor oral hygiene who showed a higher percentage of anaerobic gram-negative bacteria such as Prevotella spp. The transition of the oral microbiota to a more gram-negative dominant flora may have a distal effect of LPS-induced TLRs and trigger inflammatory cascades in the esophagus as previously described. It's also unclear whether antibiotic mouthwashes damage a healthy microbiome. Further research is needed to better define the relationship between oral hygiene and the gastrointestinal microbiota.
A recent population-based case-control study reported that poor oral health was associated with an increased risk of ESCC. More specifically, they found that tooth loss was associated with a moderate increased risk of esophageal cancer, and that brushing once a day or less was associated with an 80 percent increased risk of developing it. ESCC in this population. They propose that brushing affects the microbial balance by directly removing plaque, food residues and the carcinogenic products of tobacco and alcohol. This therefore affects inflammation levels and/or production of the carcinogenic byproducts of nitrosamine and acetaldehyde. Although this is currently theoretical, given the distance of the oral cavity from the esophagus, it is reasonable that oral hygiene would have an eventual impact on the gastrointestinal microbiota and esophageal disease as well as possible for intestinal microbiota mediated disease. Smoking:
Up to 20% of adults in the United States use tobacco products and the effect of tobacco on the gastrointestinal microbiota is uncertain. Cytological examination with esophageal balloon showed that current smoking is associated with an increase in both α and β diversity of the esophagus. It is suspected that the increase is due to smoking-related immunosuppression, which allows new bacteria to enter the upper gastrointestinal tract.
The study also showed that two types of anaerobic bacteria, Dialister invisus and Megasphaera micronuciformis, are commonly detected in current smokers. The increased α and β diversity following smoke exposure could also be a result of biofilm formation. There is some evidence that cigarette smoking induces staphylococcal biofilm formation in an oxidant-dependent manner by increasing fibronectin-binding protein-A. This leads to increased binding of staphylococci to fibronectin and increased binding to human cells.
Exposure to smoke can affect a wide range of human physiological processes by inducing a proinflammatory state, increasing cytokines such as tumor necrosis factor (TNF)-α, IL-1 , IL-6, IL-8 while reducing anti-inflammatory cytokines such as IL-10. Further investigation is needed on esophageal microbiota and its relationship with smoking and the development of disease.

Bacteriocins:
Bacteriocins are ribosome-derived peptides produced by microorganisms living in the gastrointestinal tract that are thought to have competitive flora inhibitory effects, thereby outcompeting other pathogens. In addition, in humans, bacteria are thought to maintain barrier function, participate in immunoregulatory processes, have direct antibacterial activity, and also exhibit antitumor activity. The diverse functional roles of bacteria are reflected in their broad-spectrum bactericidal properties, amino acid sequences and peptide structures, bacteriocin operon types, and different molecular weights and charges.
In a normal, healthy person, the blood-intestinal barrier is responsible for maintaining homeostasis between the blood stream and the gastrointestinal tract, ultimately regulating water and nutrient absorption. Along with the growing interest in the gastroesophageal microbiota and its relationship with the intestinal barrier, recent in vitro studies have reported that the size and properties of bacteria that allow them to cross this blood-intestinal barrier. Size and charge contribute to the movement of bacteriocins across membranes and barriers and have large roles in various physiological mechanisms.

The bacteria in the digestive tract also have strong, specific antibacterial properties. This antimicrobial property makes it essential in maintaining and influencing the composition of the local microbiome. The anticancer role of bacteria remains an area that needs further investigation. In vitro studies evaluating the effects of nisin have shown that bacteriocin can trigger apoptosis in head, neck and squamous cell carcinomas, effectively reducing the size of tumor stromal tissues.
Defensins: Defensins are small polypeptide molecules of host origin that play a role in innate immunity with both direct and indirect bactericidal effects. They serve a similar purpose to bacteriocins, but are derived from eukaryotes. Human defences are generally classified into α-defensins, which are mainly derived from neutrophils, and β-defensins, which are mainly derived from epithelial cells. Defensin expression is usually induced through cellular exposure to bacterial products such as LPS or cytokines, including TNF and IL-1. Binding of protists can lead to direct disruption of bacterial cell membranes. The positive charge of some protists is attracted to the negative components of the bacterial capsule, leading to oligomerization and pore formation. On the other hand, binding of defensin can stimulate the recruitment of an adaptive immune response.
Defensins have been shown to play a role in the normal interactions of gut bacteria.
Loss of human β-defensin (hBD) 1 and hBD3 has been implicated in the progression of EoE, and this may be the result of immune interactions between microorganisms. Unregulated defensin production can also negatively impact gut health. The production of hBD5 by hyperplastic Paneth cells, can lead to loss of E-cadherin, and thus inhibition of cell adhesion. This loss of structural integrity has been implicated in the progression of Barrett's esophagus.
Similar to bacteria, alterations in defensin structure or expression may provide a therapeutic site for altering the associated microbiome. Chimeric variants of defensin have been explored as possible antibacterial agents, but this potential therapeutic modality is still in the early stages of exploration and further work is needed to evaluate safety and their therapeutic effect.