The diverse and changing environment of the gut

Initial colonisation and succession

Bacterial colonisation of the gut occurs soon after birth (Gewolb1999). Most often, it is the mother that innoculates the newborn (vertical transmission), but the method of delivery, the milk diet and environmental factors impact the type and level of colonisation as well (Laursen2021). The infant gut is quite oxygen-rich, which initially attracts aerobic and facultative anaerobic bacteria (probably horizontally acquired), such as Enterococcus faecalis, Escherichia coli and Lactobacillus species (Mitsuoka1990, Gewolb1999, Morelli2008). However, the process of oxidative metabolism by these pioneering bugs reduces oxygen tension and allows anaerobic bacteria to become established (see Figure 1). Anaerobic Bifidobacteria and Bacteroides species are encouraged to grow by digesting prebiotic human milk oligosaccharides present in breast milk (Newburg2015), and the establishment and dominance of anaerobic bacteria in the bowel continues from this point on. From about three years of age, the child adopts a microbiome composition reflective of what they will carry during most of their adult life (Laursen2021).

Figure 1. Changes in microbial composition of key taxa over time (from Mitsuoka1990).

Most microbes live in the distal gut

The vast majority of gut bacteria catalogued in the Pubiome database have been detected in the region that stretches from the ileum to the rectum (Figure 2 & 3). A new microbe hoping to establish itself in the gut would encounter a greater variety and quantity of microorganisms the further it travelled (Figure 2). Although fewer microorganisms reside in the ileum, it still reaches one million cells per gram of luminal content. From the ileum to the caecum, the new, would-be coloniser would encounter a hundred-fold increase in microbe density, and this would continue to increase till it got to the rectum, where ten billion bacteria per gram live (Qin2010).

Movements by the bowel are important for bacterial self-seeding

The bowel excretes about 50% of the distal gut content daily (Arnoldini2018). Given that the flow of contents is unidirectional at a macroscopic level, bacteria need to find their way 'upstream' of the flow to avoid being washed out of the system. Arnoldini and coworkers suggest the most likely process for re-innoculation of fresh gut content is through peristaltic movement of the bowel (Arnoldini2018). They concluded seeding from the ileum was unlikely due to the lack of microbe diversity in this region, motility of the organisms was out of the question given that most symbionts are sessile, and innoculation from epithelial reservoirs, such as the mucus layer, would be too slow.

The work of Arnoldini and coworkers implies that limiting bowel movement could have dire consequences for gut diversity and the potential for localised extinctions of important microbe taxa. This is what appears to happen in patients recovering from opioid agonist use (known to inhibit bowel contractions) where one study showed a significant drop in microbial diversity (p = 0.006) when compared with controls (Gicquelais2020). Specifically, the researchers found a dramatic drop in the relative abundance for Bilophila (bile digesting) and Roseburia (butyrate-producing) species, and a complete absence of Prevotella (vegetable fibre munching) species.

In a similar study on mice subjected to morphine use, a noticable drop in alpha diversity was also observed compared to placebo (Wang2018a). A resulting consequence of morphine use was a ~100-fold increase in Enterococcus faecalis levels, usually a widespread commensal, but an opportunistic pathogen with links to gut dysbiosis when overgrowth occurs (leaky gut syndrome, chronic fatigue syndrome (Sheedy2009)). Importantly, though, the dysbiotic effects brought on by morphine were reversed by administration of the morphine antagonist, naltrexone (Wang2018a).

Oxygen levels influence microbiome composition

Limiting the amount of oxygen in the lumen contents of the bowel is crucial for the survival of the most important gut microbes (see Figure 3). The growth of obligate anaerobes is severely restricted by even small amounts of O₂ and yet the cells that make up the intestinal lining require the gas to respire. Here, facultative anaerobes (FA), such as Lactobacillus bacteria and Proteobacteria would play an important role in keeping oxygen levels low. There is evidence that FA bacteria occupy a niche in a mucus metabolic consortium close to the villi of the epithelium (see section on intestinal mucus). However, too many of them too close to the intestinal tissue can cause apoxia leading to inflammatory associated diseases, while too few FA and aerotolerant bacteria can lead to high oxidative stress, with resulting cell damage and dysbiosis (Singhal2020).

The gut physiology is dynamic and heterogeneous

In addition to microbe density and species richness, oxygen levels and movements of the bowel, there are other important physiological changes that occur as we travel from the ileum through to the rectum (Figure 3). The following topics have their own discussion pages: a watery and thin mucus layer in the ileum becomes thicker and more viscous toward the distal bowel (see section on intestinal mucus); glycans present as either ingested food or that provided by the host become harder to digest (see section in topic Digestion - Fate of Undigestible Carbohydrates); and the gut contents moves slower and provides more opportunities for microbe-microbe and microbe-host interations (see headings below).

Human-microbe interactions - digestion. See topics in Digestion.

Human-microbe interactions - disease. See topics in Health (to be added).

Microbe-microbe interactions. See Gut microbe symbiosis in Ecology.

Conclusion

Humans have evolved to allow - and even encourage - the growth of microbes in the gut. The ecosystem within the GI tract begins as a sterile organ containing normal levels of oxygen, a neutral pH throughout and a thin coating of epithelial mucus. As pioneering microbes are introduced, they impose extensive physiological changes to the gut. Oxygen levels in the lumen decrease, pH levels fluctuate dramatically depending on the location, and mucus thickness begins to become heterogenous. The host and key commensal bugs from the Firmicutes and Bacteroidetes phyla begin to shape the ecosystem to better optimise the breakdown of undigestible carbohydrates and proteins. Microbes have evolved to work with each other to harness nutrients from the remnants of food inaccessible to humans, and in return, produce byproducts that can be utilised by the host. This complex and dynamic ecosystem also plays a role in reducing inflammation and restricting the growth of pathogenic organisms.