The idea that the intestinal content can cause a number of physical and psychological ailments is very old (1). Remedies to clean the bowel were used in ancient Egypt, probably inspired by the peculiar behaviour of the ibis bird, as stated by Plinius (23–79 A.D.): ‘The bird which is called the ibis and which is a native of Egypt, by means of its hooked beak, laves the inside of his body by introducing water into the channel, by which it is especially necessary for health that the residuous food should be discharged’ (2). Charles-Joseph Bouchard (1837–1915) wrote a book about ‘Auto-intoxication’ in 1894 (3), and the Royal Society of Medicine discussed the role of ‘Alimentary toxæmia’ at a symposium in 1913 (4). Although these thoughts gradually fell into disrepute (5), new molecular methods to investigate the microbial ecology of the gut have been developed during the past decades (6), enabling scientists to revisit and renew old concepts (7).The human body contains about 10 times more microbes than human cells, and the gut harbours around 1,000 different bacterial species. Regarding its size and metabolic activity, the ‘microbe organ’ is comparable to the liver. Communication between microbiota and their hosts has been denoted as ‘inter-kingdom signalling’ (8), and constitute a promising research area. The gut microbial flora performs several protective, structural, and metabolic functions, and may be incriminated in a number of disorders and diseases (9). However, our understanding of the complex gastrointestinal ecosystem is in its infancy, and the ‘microbe organ’ is still largely a terra incognita.The papers included in the present thematic cluster of Microbial Ecology in Health and Disease constitute a unique collection of ongoing cutting-edge research projects. Such efforts to elucidate the role of the gut microbiome are to be congratulated. Hopefully, the results will have a major impact. The thematic cluster may also serve to illustrate an emerging understanding within gastrointestinal biology: The importance of microbes that are not there. Such microbial deprivation may be difficult to spot. Nevertheless, the implications and consequences of ‘missing microbes’ (10) are probably underestimated. In the end, we all need friends.