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Potential contributions of the host-associated gut microbiota to human physiology continue to receive extensive research interest. While various lines of evidence support a role of the microbiota in maintaining human health, perturbations in normal microbiota composition have been correlated with various dietary changes and disease states,1 particularly diarrhoea.2 We have long known that close interactions between microbiota and the host’s immune system occur in the distal small intestine and that microbes are highly metabolically active in the proximal large intestine. Recent global efforts have accumulated a wealth of data on the diversity of human gut-associated microbiota. These studies confirmed that even in healthy individuals a large degree of intraindividual as well as interindividual variation in microbiota composition and although to a lesser degree, microbial activities occur. However, what represents ‘normal’ gut microbiota is still not fully understood, which is largely due to the observed variation within and among individuals. While recent work based on phylogenetic analysis of both the small subunit (16S) of ribosomal RNA as well as metagenomic datasets suggests the existence of distinct enterotypes,3 other studies suggest more of a continuous spectrum of microbiota composition.4 ,5 Although large efforts over the last decade have advanced our understanding of microbiota composition and its unique metabolic functions, our insight into microbiota dynamics, especially when associated with life events prone to distort its composition, such as changes in transit time, nutrient availability or exposure to antibiotics, remains poorly defined.
In this issue Jalanka et al6 report on a study that determined the effects of two colon cleansing regimens, commonly used as a preparation for colonoscopy-based colorectal cancer screening, on faecal microbiota composition. While limited data on the reestablishment of gut microbiota after a colonoscopy procedure,7–9 this is the first study that compared administration of a bowel preparation solution (Moviprep), when administered in one or two doses. The authors report distinct differences of the two regimens; while the split dose decreased microbiota concentration in faeces more effectively than the single dose, indicative of a more efficient cleaning of the gut, it was associated with less distortions of microbiota composition during the recovery period.
A total of 23 individuals participated in this study, providing more statistical power for comparing microbiota compositions than the smaller previous studies. Consistent with the widely accepted hypothesis that individuals harbour distinct microbiota, samples generally clustered by individual rather than by time point. The exceptions were the samples collected immediately after lavage from five subjects. Even in those five individuals the microbiota returned to cluster with the individuals by day 14, suggesting that long-term microbiota changes were not associated with either cleansing regimen in the healthy young participants (mean age <26 years, mean body mass index=23). It is not clear that this observation would hold in other populations. Additional studies need to establish generalisability, as the large majority of the population at increased risk of colorectal cancer that is recommended to undergo gut cleansing to prep for a colonoscopy procedure falls outside these demographics. There is evidence for differences in microbiota composition in older and/or obese individuals that combined with other physiological differences in these individuals might affect their ability to effectively control microbiota distortions.
As little is known about any factors contributing to re-establish microbiota after distortions, it would be useful to identify shared characteristics that distinguish the five individuals for which microbiota clustered away from the individual after lavage. Do humans possess a distinct source for re-establishing normal microbiota after distortions in its composition? The appendix has been suggested to represent a ‘safe house 'for gut microbes.10 Gut-associated lymphatic tissue is present in the appendix, suggesting important immune functions for regulating microbiota composition. In contrast, inflammation in the appendix has been associated with local invasion by Fusobacterium nucleatum.11 To date, there is only sparse supporting evidence for the hypothesis that recolonisation of the colon after major perturbations is facilitated by microbiota harboured in the appendix. If the appendix indeed contributes to microbiota reestablishment, then individuals lacking it, due to a previous appendectomy, should show signs of delayed microbiota recovery after distortions. In developed countries the prevalence of adults having undergone appendectomies appears to be around 18%.12 The current study likely is underpowered to investigate this hypothesis and the number of participating individuals who lack an appendix wasn't reported. However, a human study that could test this hypothesis in the appropriate study population would be quite feasible.
Last, the authors appear to imply that microbiota distortions brought upon by colon cleansing have detrimental health implications. While this might be a reasonable assumption, there actually is no evidence that within what appears to be a wide range of ‘normal’, which we haven't fully defined yet, changes in microbiota negatively affect health. Indeed, changes in microbiota composition in older individuals, brought upon by colon cleansing or other more targeted means, such as intake of prebiotics/probiotics, might activate mucosal immunity by providing an exposure to different microbial luminal antigens. More detailed insights into mechanisms controlling microbiota in the gut are needed to harvest the vast potential to improve human health that the gut microbiota offers.
Contributors VM drafted the manuscript. VM and OCS revised and approved the manuscript.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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