The gut microbiome is widely recognized for its significant contribution to maintaining human health across all life stages, from infancy to adulthood and beyond. This perspective article focuses on the impacts of well-supported microbiome research on global caesarean delivery rates, breastfeeding practices, and antimicrobial use. The article also explores the impact of dietary choices, particularly those involving ultra-processed foods, on the gut microbiota and their potential contribution to conditions like obesity, metabolic syndrome, and inflammatory diseases. This perspective aims to emphasize the need for updated guidelines and policy interventions to address the increasing global trends of caesarean deliveries, reduced breastfeeding, overuse of antibiotics, and consumption of highly processed foods to counter their adverse effects on gut health.

The endocannabinoidome (eCBome) and the gut microbiota have been implicated in diet-induced obesity and impaired metabolism. While the eCBome and the gut microbiome are known to respond to diet macronutrient composition, interaction with micronutrient intake has been relatively unexplored. Iron (Fe) is an essential micronutrient for the function of enzymes involved in energy and lipid metabolism. Here, we evaluated how 28 days of Fe depletion and enrichment, in interaction with Low Fat-Low Sucrose (LFLS) or High Fat-High Sucrose (HFHS) diets, affect the host via the eCBome, and modulate intestinal gut microbial communities. Circulating levels of N-oleoyl-ethanolamine (OEA) showed an elevation associated with Fe-enriched LFLS diet, while the Fe-depleted HFHS diet showed an elevation of N-arachidonoyl-ethanolamine (anandamide, AEA) and a decrease of circulating linoleic acid. In parallel, the response of intestinal inflammatory mediators to Fe in the diet showed decreased levels of prostaglandins PGE1, PGE3, and 1a,1b-dihomo PGF2α in the caecum. Individual differences in microbial taxa were less pronounced in the ileum than in the caecum, where Eubacterium coprostanoligenes group showed an increase in relative abundance associated with Fe-depleted LFLS diets. In conclusion, our study shows that Fe intake modulates the response to the macronutrient composition of the diet in mice.

Microbial dysbiosis has been linked to environmental enteropathy (EE) and alterations in nutrient absorption; however, compositional modifications following exposure to supplementary nutrients are poorly understood. Here, we report the effect of amino acid and micronutrient supplementation on the gut microbiome of adults with EE.

In the AMAZE trial, adults with EE were randomized to amino acids (AA) and/or micronutrients (MM) for 16 weeks in a 2 × 2 factorial design against placebo. Endoscopy was performed before and after intervention, during which duodenal aspirates were collected as well as fecal samples. 16S rRNA amplicon sequencing was performed on both these samples, and differences in bacterial community composition before and after interventions were investigated using differential abundance analysis, corrected using false discovery rate, plus alpha and beta diversity measurements.

HIV seropositive participants exhibited lower alpha and beta diversity at baseline. AA and/or MM supplementation did not show significant changes in abundance or diversity of genera post-intervention compared to placebo. Micronutrient supplementation resulted in an increase in the pyruvate fermentation to acetone MetaCyc pathways compared to the placebo arm.

This study provides insights into the responsiveness of the gut microbiome to micronutrient and amino acid supplementation in adults with EE.

Non-nutritive sweeteners (NNSs) are popular sugar substitutes, valued for their potential to reduce caloric intake and associated health risks. However, their long-term effects on the human gut microbiome remain debatable. This study investigates the impact of tagatose, allulose, Rebaudioside-A (Reb-A), and saccharin on quorum-sensing (QS)-regulated phenotypes and gene expression in QS biosensor model bacteria. It sheds light on their potential influence on the gut microbiome. Our study revealed diverse effects among the NNSs. Tagatose and allulose demonstrated QS phenotypic inhibition in Chromobacterium violaceum (≈50%) and Pseudomonas aeruginosa (20–50%) in a concentration-dependent manner. Additionally, tagatose and allulose decreased the P. aeruginosa lasI gene expression. Reb-A and saccharin presented a significant, however less prominent, phenotypic inhibition on C. violaceum (25–30%) and P. aeruginosa swarming motility (≈20%). Both NNSs decreased the expression of the lasI gene of P. aeruginosa. Molecular docking of QS regulatory proteins showed that saccharin and Reb-A have significantly higher binding affinity compared to allulose and tagatose, relative to native inducers. These results suggest the complex interactions mediated by NNSs in QS regulatory pathways. These findings provide valuable insights into the varied, species and dose-dependent effects of NNS on microbial communication, suggesting potential implications for the gut microbiome.