**7. The Association between Nut Intake and Gastrointestinal Microbiota**

The relationship between gut microbiota (GM), diet, and healthy aging has been established in many studies [193–195]. Nutrition is a vital instrument in keeping a friendly microbiome, and this is more important in aging, when increased usage of medication can reduce healthy GM diversity and stability [196]. GM can impact CNS function, via gut-brain axis, and regulate the immune system [197,198]. Also, GM can be involved in several brain disorders (autism, PD, schizophrenia) [199]. Patients having PD, a high incidence neurodegenerative disorder among those over 60 years old, revealed pro-inflammatory bacteria in their gastrointestinal tract. Pathological by-products of these microorganisms could leak from the intestinal lumen in the enteric nervous system and aggregate into insoluble fibrils in the CNS [200,201].

Nut polyphenols were reported to increase the abundance of *Bifidobacterium* and *Lactobacillus* bacteria, probiotic strains related to significant lowering of CRP concentrations and increase in plasma HDL-C, cancer prevention, immune-modulation, as well as reductions of pathogenic *Clostridium* species and enteropathogens *Salmonella typhimurium* or *Staphylococcus aureus* [202,203]. Walnut ingestion increased the abundance of *Lactobacillus* [204], while decreasing microbial derived, proinflammatory LDL-C and secondary bile acids in healthy mature adults [205]. Similar results were achieved in a very recent 8-week long RCT, including 194 healthy individuals (mean age 63 years), where after 43 g/day walnut-enriched diet, the probiotic and butyric acid-producing species (*Ruminococcaceae* and *Bifidobacteria*) significantly increased (*p* < 0.02), while *Clostridium* species significantly decreased (*p* < 0.05) [206]. Also, pistachio and almond consumption via the prebiotic compounds may stimulate the growth of beneficial butyrate-producing bacteria and inhibit the development of pathogenic ones [207]. Holscher et al. [208] demonstrated that daily consumption of around 42 g almonds for at least 3 weeks can increase the abundance of *Roseburia* species, a favorable genus known to be negatively affected by age.

The favorable effect of walnut diets on BP may be linked to changes in the GM. As walnuts are not completely metabolized in the upper gastrointestinal tract, they provide substrate to the gut microbiome and may stimulate the production of short-chain fatty acids, including butyrate, which have been associated with normal BP management [209].

Human diet influences the relative abundance of bacterial communities present in the gastrointestinal tract [210]. A significant diversity and number of bacteria ensure a greater ability to resist metabolic changes and infections and constitute the prerequisite for a healthy status of the gut [202]. Consequently, a nut enhanced diet characterized by high antioxidant and anti-inflammatory activities can delay age-related microbiota changes and positively alter the microbial composition of the human GM with benefits for health.
