Metagenomic Analysis of the Human Distal Gut Microbiome

Abstract

The human intestinal microbiota is composed of 10 13 to 10 14 microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own genome. We analyzed ~78 million base pairs of unique DNA sequence and 2062 polymerase chain reactionamplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-Derythritol 4-phosphate pathway-mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.Our body surfaces are home to microbial communities whose aggregate membership outnumbers our human somatic and germ cells by at least an order of magnitude. The vast majority of these microbes (10 to 100 trillion) inhabit our gastrointestinal tract, with the greatest number residing in the distal gut, where they synthesize essential amino acids and vitamins and process components of otherwise indigestible contributions to our diet such as plant polysaccharides (1). The most comprehensive 16S ribosomal DNA (rDNA) sequencebased enumeration of the distal gut and fecal microbiota published to date underscores its highly selected nature. Among the 70 divisions (deep evolutionary lineages) of Bacteria and 13 divisions of Archaea described to date, the distal gut and fecal microbiota of the three ‡

Probiotics drive gut microbiome triggering emotional brain signatures

“…1 , 2 The ‘gut-brain axis‘ had already been studied before this field of research gained new momentum a decade ago with the characterization of the gut microbiome. 3 Although the underlying molecular mechanisms remain elusive, the gut microbiota has been shown to modulate behavior and brain processes, including pain perception, 2 stress responsiveness, 4 prefrontal myelination, 5 and brain biochemistry. 1 Experimental manipulation of the gut microbial community composition was shown to be able to modify the host's neural function.…”

The regulation of host defences to infection by the microbiota

“…It contains approximately 10 13 –10 14 bacteria that colonize environmentally exposed surfaces 3, 4. Colonization begins in earnest after birth, with the mother normally providing the bacterial inoculum that seeds the microbiota of her offspring 4, 5.…”

“…Initially, the bacterial communities of each surface have a similar taxonomic composition, but through the course of infancy each surface develops a microbiota with a unique composition that stabilizes during adulthood 2, 6, 7. In the adult gastrointestinal tract, the microbiota is dominated by bacteria from two phyla: the Bacteroidetes and Firmicutes 3. There are representatives from other bacterial phyla, including Proteobacteria and Acintobacteria, but they form only a minor fraction of the bacterial taxa present 1, 3.…”

An Improved Methodology to Overcome Key Issues in Human Fecal Metagenomic DNA Extraction

“…The total number of microbes residing in the human body, especially in the gut, outnumbers that of human cells [3]. A vast array of recent studies has identified many microbial enterotypes in the human gut [4], [5], [6], [7], [8], [9], [10] and their potential roles in immunity [5], [7], [8], development [8], digestion [9], and other functions [10].…”

“…Majority of the studies have used 16S rRNA gene sequencing to understand the community structure, composition, and functional diversity of the human gut microbiome [1], [2], [3], [4]. The success of these culture-independent studies depends primarily on the quality and quantity of metagenomic DNA isolated from the given samples [11], [12], [13].…”