The intestinal microbiota in health and disease

Over the last years, there has been increasing interest in the intestinal microbiota internationally and in New Zealand. As an illustration of this, more than 26,000 items were selected on a current search of PubMed in April 2020 using a single search term ‘intestinal microbiota’. Furthermore, almost half of these items (10,250) were published in the last 24 months.

With the development of more advanced tools, especially non-culture-based techniques (Blanco-Míguez et al. 2019), there has been increasing interest not only in the world of the intestinal microbiota but also of the wide-ranging impacts of the components of this world upon human health and disease. In the past culture-based methods enabled us to learn much about the intestinal microbiota. Using an analogy of learning about the ocean, this approach could be compared to a child splashing in the waves along the seashore, or a sailor looking down into the depths from his ship. New methods and tools, such as high-throughput DNA sequencing, have enabled us to extend our knowledge and understanding in greater molecular detail: similar to being able to explore the depths of the ocean. However, while we have started to understand the complexities and importance of this ecosystem, we still have much to learn before we unlock all the secrets held therein (Almeida et al. 2019).

The intestinal microbiota develops from the time of birth (and perhaps earlier), with fine-tuned mechanisms that assist in the appropriate development of suitable organisms whilst prompting host responses along the way. These mechanisms include the interactions between human milk oligosaccharides, milk-derived organisms, and the optimised growth of bifidobacterial species in the infant’s gut (Lugli et al. 2020; Wiciński et al. 2020).

Two articles in this special issue examine different aspects of these critical early life events. Ali et al. (2020) outline key processes involved in the early development of the intestinal microbiota. They delineate aspects of a putative ideal microbiota and emphasise how perturbations of this could contribute to disease in later life, such as atopic disease and inflammatory bowel disease. Kim and co-authors (Kim et al. 2020) also focus on the early steps in the development of the microbiota and emphasise the impact of complementary foods fed to infants during weaning. These two reviews focus on different aspects of these early events, but both serve to remind us of the critical importance of early life events and, most importantly, the possible impact of variations in these events upon future and life-long health and disease.

The early acquisition of specific organisms throughout the gut is explored in several other articles in this special issue. Signal et al. (2020) outline the importance of the acquisition of the gastric bacterium, Helicobacter pylori. This bacterium is typically acquired in the first years of life from a previously-colonised close family member. Maternal acquisition is more common, with gastro-oral or faecal-oral transmission considered possible. After initial colonisation, this bacterium establishes itself in the gastric environment, where it has developed key strategies to survive in this harsh acidic setting. While most individuals colonised with H. pylori have asymptomatic and uncomplicated chronic gastritis, some develop peptic ulceration and a smaller number progress to develop gastric cancer or lymphoma. Signal and colleagues (Signal et al. 2020) explore the patterns of H. pylori-related outcomes in New Zealand (especially in regards to gastric cancer) and discuss possible preventative strategies with an NZ perspective.

Similarly, Keenan and Frizelle (2020) discuss particular toxigenic bacteria that are acquired early in life but may also persist for decades and prompt the subsequent development of colonic carcinoma, one of the most common types of cancer seen in New Zealanders. Particular toxigenic strains of Bacteroides fragilis may contribute to this disease. Other co-factors, such as diet and interactions with other bacteria, are likely to also be important in these outcomes.

The interactions between diet and the intestinal microbiota cannot be underestimated, along the lines of the colloquial saying – we are what we eat. Key studies have demonstrated marked differences in the predominant organisms present in stools from hunter-gatherers eating a fibre-rich, plant-based diet compared to individuals living in an urban developed country (Gupta et al. 2017). Further, marked changes in diet can promptly lead to changes in the patterns of bacteria that thrive under these environmental changes (Parris et al. 2019; Wilson et al. 2020).

Along these lines, the article by Tannock and Liu (2020) outlines the processes whereby dietary fibre prompts changes in the production of short-chain fatty acids, such as butyrate and propionate, by the microbiota. Butyrate is a key nutrient for colonocytes, and likely has further beneficial intestinal and extra-intestinal roles as a signalling molecule in microbiota-human interactions. Propionate also has a signalling role in human physiology and is important in enhancing satiety; of particular interest in understanding obesity and other metabolic conditions, another common long-term health issue in NZ.

Whilst dietary fibre can have prebiotic effects, a further way to modify the patterns of the organisms within the intestinal microbiota is the therapeutic use of probiotics – organisms that can generate beneficial effects upon administration (Abid and Koh 2019). There has been much interest in the benefits of probiotics in the lay community, but few data to support the use of such agents in specific medical conditions. Crane et al. (2020) in this issue, outline some of the background of probiotics and refer specifically to work conducted in NZ demonstrating that the administration of probiotics in the first years of life generates reductions in allergic disease in the children and also leads to additional benefits for the mothers of these children.

Finally, Heenan et al. (2020) examine the relevance of the intestinal microbiota in the setting of irritable bowel disease (IBS), a common functional disorder leading to significant morbidity in New Zealanders. Perturbations of the intestinal microbiota following an enteric infection, such as Campylobacter pylori, are noted to lead to increased rates of IBS (Svendsen et al. 2019). These observations lead us to further understand the importance of the fine-tuned balance within the community of the intestinal microbiota and also to demonstrate the close relationships between the microbiota, the enteric nervous system and intestinal motility, highlighting the likelihood that these interactions are not isolated to immediate relationships within the gut, but may also involve the gut-brain axis and other body systems.

Whilst this special issue has focused on a number of key aspects of the roles, function and importance of the intestinal microbiota, there remain numerous other areas of tremendous relevance and interest. These include the increasing recognition of the contributions of the intestinal microbiota to various conditions ranging from depression and anxiety to diabetes and obesity (Das and Nair 2019; Eltokhi et al. 2020). Whilst we have advanced from the analogy of the child splashing amongst the waves, we are still ignorant of the full and deep secrets of the intestinal microbiota. We look forward to further advances of understanding about this intriguing and critically-important community within us all.

Disclosure statement

No potential conflict of interest was reported by the author(s).

ORCID

Andrew S. Day http://orcid.org/0000-0003-2290-7386

Jacqueline I. Keenan http://orcid.org/0000-0002-3409-0337

Gerald W. Tannock http://orcid.org/0000-0002-9197-733X