Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides , with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria , Actinobacteria , and Faecalibacteria . The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

The concept that the gut microbiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gut microbiota may be useful in treating stress-related disorders and metabolic diseases.

Aims To assess the ability of human intestinally derived strains of Lactobacillus and Bifidobacterium to produce γ‐aminobutyric acid (GABA). Methods and Results Strains of Lactobacillus and Bifidobacterium were grown in medium containing monosodium glutamate (MSG). Growth of the bacteria and conversion of MSG to GABA were measured. Of 91 intestinally derived bacteria assessed, one Lactobacillus strain and four strains of Bifidobacterium produced GABA. Lactobacillus brevis DPC6108 was the most efficient of the strains tested, converting up to 100% of MSG to GABA. The ability of the cultured intestinal strains to produce GABA was investigated using a simple pH‐controlled anaerobic faeces‐based fermentation, supplemented with 30 mg ml⁻¹ MSG. The addition of Lact. brevis DPC6108 to a faeces‐based fermentation significantly increased the GABA concentration (P < 0·001), supporting the notion that this biosynthesis could occur in vivo. Conclusions The production of GABA by bifidobacteria exhibited considerable interspecies variation. Lactobacillus brevis and Bifidobacterium dentium were the most efficient GABA producers among the range of strains tested. The addition of Lact. brevis DPC6108 to the culturable gut microbiota increased the GABA concentration in fermented faecal slurry at physiological pH. Significance and Impact of the Study Identification of optimal MSG conversion to GABA by particular cultured elements of the commensal intestinal microbiota and the demonstration that this can occur under simulated in vivo conditions offer new prospects for microbiota modulation to promote health.