**Background:** The gut microbiota plays a key role in human health by degrading food, releasing metabolites, detoxifying compounds, and modulating immunity. It is influenced by age, diet, physical activity, and antibiotic use. Despite growing recognition that microbes are integral to human health, there has been no conjoint recommendation for dietary compounds that complement ingested organisms to promote improved health outcomes. This narrative review discusses how beneficial microbes—probiotics, fermented foods, and donor feces—are being used to manage health, and explores the rationale for selecting microbial strains and aligning diets to support their gut propagation.
**Methods:** The PubMed database was searched for relevant articles using keywords related to nutrition, physical activity, microbes, and health, combined with Boolean operators. The review covers FMT, aging and the microbiome, the gut-brain axis and physical activity, nutrition and the microbiome, and strain alignment with host health. A pilot clinical trial design is presented for PKU, the most common inborn error of amino acid metabolism.
**Key Results:** FMT has successfully resolved recurrent *Clostridioides difficile* infection, including in patients with inflammatory bowel disease. In a small cohort of 13 individuals who received FMT for recurrent *C. difficile*, 80% of pre-FMT strains were eliminated 5 years post-FMT despite no dietary alignment with the donor. A large study of over 1000 Chinese people aged from youths to centenarians showed that the microbiota of centenarians was remarkably similar to people over 30, suggesting maintenance of a health-promoting gut microbiota through life is feasible. A Mediterranean diet in the elderly altered the gut microbiome, resulting in more short/branch-chained fatty acids and lower toxic compounds, decreasing markers of frailty and inflammation and increasing cognitive function. In insulin-resistant participants, sprint interval or moderate-intensity continuous training resulted in beneficial gut microbial changes, including a decreased ratio of Firmicutes/Bacteroidetes, *Clostridium*, and *Blautia*, and increased Bacteroidetes two weeks after training. In Finnish cross-country skiers, *Butyricicoccus* was positively associated with HDL cholesterol, HDL2 cholesterol, and HDL particle size. A 17-week randomized prospective study of plant-based fiber and fermented foods (six servings/day of kombucha, yogurt, kefir, buttermilk, kvass, kimchi, sauerkraut, other fermented veggies, and/or vegetable brine drink) found that inflammatory markers decreased and microbial diversity increased in the fermented food group. A 14-day intervention study showed no changes in gut bacteria when humans consumed non-nutritive sweeteners at a dose equivalent to three 355 mL cans of diet beverage daily. The emulsifier carboxymethylcellulose was shown to reduce gut microbiota diversity and be associated with lower levels of short-chain fatty acids and free amino acids. A pilot study found that after consuming a Westernized fast-food diet for four days, the gut composition closely resembled what has been associated with chronic disease, whereas a Mediterranean diet showed the opposite.
**Clinical Implications:** The authors argue that FMT and probiotic interventions are rarely paired with dietary strategies to support the engraftment and function of beneficial organisms. They note that the standard criteria for selecting fecal donors do not consider the donor's microbiota composition or its metabolic implications for the recipient. The proposed PKU pilot study—an open-label, single-arm trial of 20 individuals receiving *Escherichia coli* Nissle 1917 and *Lactocaseibacillus rhamnosus* GG with daily exercise (≥10,000 steps) for 12 weeks—illustrates how future research could integrate probiotics, diet, and exercise while using omics technologies to measure changes in neuroactive biogenic amines and gut microbiota composition. The authors conclude that human interventional studies are urgently needed to test specific microbes with dietary intakes that encourage the growth of desired organisms and metabolites for each individual's primary health issue.