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Factors able to modify gut microbiota include different medications. Antibiotics are expected to have a large effect, but also other common medications can have an impact on gut microbiota composition. Proton-pump inhibitors (PPIs) are, for example, associated with a higher Streptococcaceae and Micrococcaceae abundance and a lower microbiota diversity. Also, paracetamol and opioids are associated with an increase of Streptococcaceae, whereas serotonin reuptake inhibitors (SSRIs) are negatively associated with Turicibacteraceae. Moreover, inhaled anticholinergics are negatively associated with Ruminococcaceae and Peptococcaceae abundance and microbiota diversity. Herbs can modulate gut microbiota too. For example, ginseng administration has been associated with the decrease in bacteria that possibly promote tumorigenesis (such as Bacteroidales and Verrucomicrobia) and an increase in bacteria that possibly exert antiinflammatory and anti-cancer activities (such as Firmicutes).

Diet is another major regulator of gut microbiota structure and function. Its contribution to microbiota modulation and host-microbiota crosstalk is evident from the beginning of life, with human milk oligosaccharides participating in microbiota development and solid food introduction increasing bacterial richness. However, in the elderly, where food diversity is reduced, microbiota richness decreases, too. Some nutrients (such as glycans, quinones, and flavonoids) directly interact with bacteria, promoting or inhibiting their growth. Moreover, dietderived compounds can indirectly shape gut microbiota by affecting host metabolism and the immune system. Vitamin D, for example, is associated with a decrease in circulatory levels of LPS, decreased abundance of Coprococcus and Bifidobacterium, and increased abundance of Prevotella, and dietary constituents (such as selected emulsifiers) might disrupt the intestinal barrier.

Carbohydrate restriction and diets rich in fiber and vegetables are associated with health benefits due, at least in part, to gut microbiota changes. High amounts of plant polysaccharides in the diet are associated with a low abundance of Firmicutes and a high abundance of Bacteroidetes (specifically Prevotella), whereas a paucity of dietary fiber is associated with the increase of Enterobacteriaceae (specifically Shigella and Escherichia). The absence of dietary fiber is instead associated with an increase in mucusdegrading bacteria (Akkermansia muciniphila and Bacteroides caccae) at the expense of fiber-degrading species (Bacteroides ovatus and Eubacterium rectale). That is why microbiota is responsive to some dietary interventions; for example, in overweight and obese people the consumption of fruits, vegetables, and fish is associated with microbiome richness.

This is why the intake of prebiotics, probiotics, and synbiotics (the latter combining prebiotics with probiotics) has long been proposed as a way of modifying metabolic disorders largely dependent upon altered microbiota composition. Applying personally tailored diets is associated with shifts in gut microbiota composition after only 1 week of intervention. Prebiotics are substances enhancing gut bacteria growth or activity. Among them are non-digestible dietary fibers (present in many fruits and vegetables) that are fermented by gut bacteria into SCFAs, and phytoestrogens (present, for example, in some berries). SCFAs, especially butyrate, help maintain intestinal immune homeostasis and protect from inflammation and carcinogenesis. Moreover, fiber seems to promote intestinal barrier function and improve glucose tolerance. Prebiotic intake can significantly reduce body weight, body fat percentage, and desire for high-calorie foods.

It may also improve insulin sensitivity, low-grade chronic inflammation, and lipid metabolism. Prebiotics can be administered in the form of fermentable dietary fiber such as inulin, oligofructose, fructooligosaccharides, or galactooligosaccharides, which can increase the abundance of bifidobacteria and lactobacilli, although not exclusively. Also, other substances like conjugated linoleic acid and milk sphingomyelin exert prebiotic activities. Probiotics are instead live bacteria providing health benefits when consumed. They include lactobacilli and bifidobacteria and can be easily found both in fermented foods (such as yogurt and kefir) and in food supplements. Dietary supplements with bacterial strains aim at replenishing the gut with healthy commensal bacteria granting favorable metabolic properties.

They exert several and sometimes very different beneficial effects. In some cases, they can help reduce intestinal pain, bloating or tension, or attenuate the immune responses associated with acute colitis symptoms. Moreover, it seems that probiotics can help improve the intestinal barrier and inhibit pathogens growth. Given the central role played by gut microbiota in the brain-gut axis, probiotics can also help in cases of psychological diseases; specifically, they can reduce stressassociated visceral hypersensitivity, and lactobacilli and bifidobacteria can help fight anxiety and depression. Strain mixtures might be more effective than some single-strain preparations.