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therapeutic index, meaning a small increase in blood concentration can be the difference between a therapeutic
effect and toxicity. The interaction caused by grapefruit compounds can last for up to 24 hours and is most
potent when the juice is ingested with the drug or up to 4 hours prior.

Mechanism of Grapefruit - drug interaction: a) CYP3A4 Inhibition: Grapefruit contains
furanocoumarins, which inhibit the CYP3A4 isoform of cytochrome P450 in the intestine. This enzyme is
responsible for metabolizing many drugs. b) P-glycoprotein (Pgp) Inhibition: Grapefruit also inhibits P-
glycoprotein, a transporter that pumps lipophilic molecules out of intestinal epithelial cells and back into the
intestinal lumen.

Examples Grapefruit - drug interactions:

    • Amiodarone (Cordarone®) - anti-arrhythmic drug.
    • Simvastatin (Zocor®) - cholesterol-lowering drug.
    • Buspirone (Buspar®) - anxiolytic.

                         Prebiotics, Probiotics and Synbiotics

The human intestine contains a vast microbiota of ~100,000 billion bacteria, located mainly in the colon and
comprising hundreds of species. Most bacterial cells in fecal specimens cannot be grown in culture. The
microbial diversity between individuals is remarkable; each person has a distinctive bacterial composition,
determined by host genotype and initial colonization at birth.

A century ago, Elie Metchnikoff postulated that lactic acid bacteria (LAB) offered health benefits and could
promote longevity. He suggested that modifying the gut microbiota to replace proteolytic microbes (like
Clostridium, which produce toxins) with useful microbes could suppress "intestinal auto-intoxication" and the
resulting aging.

In 1917, before penicillin's discovery, Professor Alfred Nissle isolated a nonpathogenic Escherichia coli strain
from a soldier who did not develop enterocolitis during a severe shigellosis outbreak. Intestinal tract disorders
were often treated with viable nonpathogenic bacteria to replace or change the intestinal microbiota.

Henry Tissier first isolated a Bifidobacterium from a breast-fed infant, naming it Bacillus bifidus communis.
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