There is good evidence that the complex microbial flora present in the gastrointestinal tract of all warm-blooded animals is effective in providing resistance to disease. However, the composition of this protective flora can be altered by dietary and environmental influences, making the host animal susceptible to disease and/or reducing its efficiency of food utilization. What we are doing with the probiotic treatments is re-establishing the natural condition which exists in the wild animal but which has been disrupted by modern trends in conditions used for rearing young animals, including human babies, and in modern approaches to nutrition and disease therapy. These are all areas where the gut flora can be altered for the worse and where, by the administration of probiotics, the natural balance of the gut microflora can be restored and the animal returned to its normal nutrition, growth and health status.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2672.1989.tb05105.x

Probiotics in man and animals

Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria

Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.

Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

/pdf/induction-of-colonic-regulatory-t-cells-by-indigenous-3lbzi76jax.pdf

Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

The fecal flora of 35 breast-fed and 35 bottle-fed babies was determined. Bifidobacteria were the predominant fecal bacteria in both groups. Conversely, the counts of most of the other bacteria, such as bacteroides, eubacteria, peptococci, veillonella, clostridia, enterobacteria, streptococci, and bacilli in the bottle-fed group were significantly higher than those in the breast-fed group. The frequencies of occurrence of lecithinase positive Clostridia, clostridia-others, pseudomonas and bacilli in the bottle-fed group were significantly higher than those in the breast-fed group. Twenty-one genera and 103 species or biovars of microorganisms were isolated from the feces of the breast-fed group and 20 genera and 97 species or biovars from the bottle-fed group. The organism that showed the highest number and the highest frequency of occurrence in both groups was Bifidobacterium breve. Bifidobacterium infantis, which was formerly the most prevalent Bifidobacterium species in baby feces, was never isolated in this study. Further, the counts and incidences of Clostridium paraputrificum, C. perfringens, and Bacillus subtilis, the counts of C. clostridiiforme, Bacteroides vulgatus, Veillonella parvula, Lactobacillus acidophilus, Escherichia coli, Streptococcus bovis, S. faecalis, and S. faecium and the incidences of C. difficile, C. tertium, and Pseudomonas aeruginosa in the bottle-fed infants were significantly higher than those in the breast-fed infants.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1348-0421.1984.tb00754.x

The Intestinal Microflora of Infants: Composition of Fecal Flora in Breast-Fed and Bottle-Fed Infants

There is a growing consensus on the beneficial effects of bifidobacteria in human health. It is now clear that bifidobacteria that exist in the large intestine are helpful for maintenance of human health and are far more important thanLactobacillus acidophilus as beneficial intestinal bacteria throughout human life. In other words, the reduction or disappearance of bifidobacteria in the human intestine would indicate an “unhealthy” state. Oral administration of bifidobacteria may be effective for the improvement of intestinal flora and intestinal environment, for the therapy of enteric and hepatic disorders, for stimulation of the immune response, and possibly for the prevention of cancer and slowing the aging process. However, for consistent and positive results further well-controlled studies are urgently needed.

Bifidobacteria and their role in human health.

Effect of a probiotic formula on intestinal immunoglobulin A production in healthy children

Fructo-oligosaccharides are widely distributed in plants such as onions, asparagus, wheat etc., and obtained from sucrose by the action of fructosyltransferase. They are not hydrolyzed by human digestive enzymes, but are utilized by intestinal bacteria such as bifidobacteria. Bacteroides fragilis group, peptostreptococci and klebsiellae. In the experiment with 23 patients (73 +/- 9 years old), improvement of fecal microflora was observed by oral administration of fructo-oligosaccharides 8 g per day for two weeks: the population of bifidobacteria in feces increased about 10 times compared before the administration; average pH of stool showed 0.3 lower than that before administration.

Effect of fructo‐oligosaccharides on intestinal microflora

The history of intestinal microecology began in 1719, when the first microscopic observations of fecal bacteria were made by Leeuwenhoek. In 1885, Escherich initiated the study of the intestinal flora with a description of Bacterium coli communior in bottle-fed infants. Subsequent studies on intestinal microecology have mainly been focussed on the aerobes, such as coliform bacteria, enterococci, etc.

Tomotari Mitsuoka

Papers

The Intestinal Microflora of Infants: Composition of Fecal Flora in Breast-Fed and Bottle-Fed Infants

Bifidobacteria and their role in human health.

Effect of a probiotic formula on intestinal immunoglobulin A production in healthy children

Effect of fructo‐oligosaccharides on intestinal microflora

Recent Trends in Research on Intestinal Flora