No abstract

Environment and diet are two major factors affecting the human gut microbiome. In this study, we used a pig model to determine the impact of these two factors during lactation on the gut microbiome, immune system, and growth performance. We assigned 80 4-day-old pigs from 20 sows to two rearing strategies at lactation: conventional rearing on sow’s milk (SR) or isolated rearing on milk replacer supplemented with solid feed starting on day 10 (IR). At weaning (day 21), SR and IR piglets were co-mingled (10 pens of 4 piglets/pen) and fed the same corn-soybean meal-dried distiller grain with solubles- and antibiotic-free diets for eight feeding phase regimes. Fecal samples were collected on day 21, 62, and 78 for next-generation sequencing of the V4 hypervariable region of the bacterial 16S rRNA gene. Results indicate that IR significantly increased swine microbial diversity and changed the microbiome structure at day 21. Such changes diminished after the two piglet groups were co-mingled and fed the same diet. Post-weaning growth performance also improved in IR piglets. Toward the end of the nursery period (NP), IR piglets had greater average daily gain (0.49 vs. 0.41 kg/d; P < 0.01) and average daily feed intake (0.61 vs. 0.59 kg/d; P < 0.01) but lower feed efficiency (0.64 vs. 0.68; P = 0.05). Consequently, IR piglets were heavier by 2.9 kg (P < 0.01) at the end of NP, and by 4.1 kg (P = 0.08) at market age compared to SR piglets. Interestingly, pigs from the two groups had similar lean tissue percentage. Random forest analysis showed that members of Leuconostoc and Lactococcus best differentiated the IR and SR piglets at weaning (day 21), were negatively correlated with levels of Foxp3 regulatory T cell populations on day 20, and positively correlated with post-weaning growth performance. Our results suggest that rearing strategies may be managed so as to accelerate early-life establishment of the swine gut microbiome to enhance growth performance in piglets.

The human microbiota and epigenetic processes have both been shown to play a crucial role in health and disease. However, there is extremely scarce information on epigenetic modulation of microbiota members except for a few pathogens. Mainly DNA adenine methylation has been described extensively in modulating the virulence of pathogenic bacteria in particular. It would thus appear likely that such mechanisms are widespread for most bacterial members of the microbiota. This review will present briefly the current knowledge on epigenetic processes in bacteria, give examples of known methylation processes in microbial members of the human microbiota and summarize the knowledge on regulation of host epigenetic processes by the human microbiota.

The gut-brain axis may contribute to the pathophysiology of neurodevelopmental disorders, yet it is often unclear how risk genes associated with these disorders affect gut physiology in a manner that could impact microbial colonization. We addressed this question using Drosophila melanogaster with a null mutation in kismet, the ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, CHD7 and CHD8 are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found kismet mutant flies have a significant increase in gastrointestinal transit time, indicating functional homology of kismet with CHD7/CHD8 in vertebrates. To measure gut tissue mechanics, we used a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision, which revealed significant changes in the mechanics of kismet mutant guts, in terms of elasticity, strain stiffening, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found kismet mutants have reduced diversity of gut microbiota at every taxonomic level and an increase in pathogenic taxa. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and measured courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of gut microbiome in the control strain reduced courtship activity. This result demonstrated that antibiotic treatment can have differential impacts on behavior that may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-brain axis to influence behavior. Based on our results, we also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neuronal development.