Metagenomic analysis of environmental and clinical samples is gaining considerable importance in today's literature. Changes in the composition of the intestinal microbial communities, relative to the healthy control, are reported in numerous conditions.We have carefully analyzed the frequencies of the short nucleotide sequences in the metagenomes of two different enterotypes; namely of Chinese and European origins.We have identified 255 nucleotide sequences of length up to 9, such that their frequencies significantly differ in the two enterotypes examined.We have demonstrated that short nucleotide sequences are capable of differentiating enterotypes, and not only metagenomes, originating from healthy and diseased subjects.Our results may imply that the frequency-differences of certain short nucleotides have diagnostical value if properly applied for different clusters of metagenomes. "This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo".