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Dry eye is a common ocular disorder with complex pathophysiology that extends beyond tear deficiency and inflammation. Despite growing evidence of host-microbiome interactions at mucosal surfaces, the contribution of the ocular surface (OS) microbiome to dry eye remains poorly understood. Our findings in this study reveal that shifts in specific taxa and ecological interactions correlate with improvements in meibomian gland function and dry eye symptoms, even in the absence of major changes in overall microbiota. By identifying microbial signatures potentially linked to clinical improvement, we provide systems-level insight into the role of low-biomass microbiomes in ocular health. This work expands the current understanding of microbiome-host dynamics in non-gut environments and supports future development of microbiome-informed therapeutic strategies. This study is registered with ClinicalTrials.gov as NCT06936462 .

Abstract The present study aimed at investigating the impact of heat challenges on gut microbiota composition in growing pigs and its relationship with pigs’ performance and thermoregulation responses. From a total of 10 F1 sire families, 558 and 564 backcross Large White × Créole pigs were raised and phenotyped from 11 to 23 wk of age in temperate (TEMP) and in tropical (TROP) climates, respectively. In TEMP, all pigs were subjected to an acute heat challenge (3 wk at 29 °C) from 23 to 26 wk of age. Feces samples were collected at 23 wk of age both in TEMP and TROP climate (TEMP23 and TROP23 samples, respectively) and at 26 wk of age in TEMP climate (TEMP26 samples) for 16S rRNA analyses of fecal microbiota composition. The fecal microbiota composition significantly differed between the 3 environments. Using a generalized linear model on microbiota composition, 182 operational taxonomic units (OTU) and 2 pathways were differentially abundant between TEMP23 and TEMP26, and 1,296 OTU and 20 pathways between TEMP23 and TROP23. Using fecal samples collected at 23 wk of age, pigs raised under the 2 climates were discriminated with 36 OTU using a sparse partial least square discriminant analysis that had a mean classification error-rate of 1.7%. In contrast, pigs in TEMP before the acute heat challenge could be discriminated from the pigs in TEMP after the heat challenge with 32 OTU and 9.3% error rate. The microbiota can be used as biomarker of heat stress exposition. Microbiota composition revealed that pigs were separated into 2 enterotypes. The enterotypes were represented in both climates. Whatever the climate, animals belonging to the Turicibacter–Sarcina–Clostridium sensu stricto dominated enterotype were 3.3 kg heavier (P < 0.05) at 11 wk of age than those belonging to the Lactobacillus-dominated enterotype. This latter enterotype was related to a 0.3 °C lower skin temperature (P < 0.05) at 23 wk of age. Following the acute heat challenge in TEMP, this enterotype had a less-stable rectal temperature (0.34 vs. 0.25 °C variation between weeks 23 and 24, P < 0.05) without affecting growth performance (P > 0.05). Instability of the enterotypes was observed in 34% of the pigs, switching from an enterotype to another between 23 and 26 wk of age after heat stress. Despite a lower microbial diversity, the Turicibacter–Sarcina–Clostridium sensu stricto dominated enterotype was better adapted to heat stress conditions with lower thermoregulation variations.

In human-altered landscapes, animals face numerous threats to their survival, yet little is known about how rapid environmental change affects host–microbiome dynamics across generations. Microbial communities play critical roles in host nutrition, immunity, and overall fitness, and shifts in composition may alter an organism’s ability to adapt. We examined the gut microbiota of the endangered Pacific pocket mouse during the transition from wild to captive environments and across four descendant generations. We found that the microbiome did not immediately shift with captivity but instead stabilized into a distinct, captivity-associated state only after several generations. This study provides the first characterization of gut microbiota in pocket mice and is the first to show, at this resolution, how a wildlife species’ microbiome adapts to environmental change while tracking health and fitness across generations. Our findings highlight the need to incorporate microbiome dynamics into conservation breeding and management strategies.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant ( P  < 5 × 10 −8 ) threshold. One locus, the lactase ( LCT ) gene locus, reached study-wide significance (genome-wide association study signal: P  = 1.28 × 10 −20 ), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 −10  <  P  < 5 × 10 −8 ) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations.

Gut microbial metabolic activities play important roles in human health, prompting interest in the discovery of gut microbiome-targeted small molecule inhibitors as potential therapeutics. Anaerobic choline metabolism by the gut microbiome generates trimethylamine and its downstream metabolite trimethylamine- N -oxide (TMAO), which cause trimethylaminuria and are correlated with cardiometabolic diseases, respectively. Current strategies for modulating microbial metabolism with small molecule inhibitors typically require having a target enzyme. Here, we show that a growth-based phenotypic screen can identify inhibitors of choline metabolism with chemical scaffolds that are structurally distinct from choline and existing inhibitors. The resulting optimized compounds lower serum TMAO in gnotobiotic mice without significantly perturbing gut microbiome composition. This work highlights the potential of using phenotypic screening to rapidly discover additional inhibitors of microbial metabolic activities, which would accelerate mechanistic studies of the microbiome and deepen our understanding of disease biology from correlation to causation.

This study provides the first comprehensive analysis of gut microbiome development in Icelandic children, covering the time from before the introduction of solid foods to 5 years of age. Although the overall developmental patterns of the gut microbiome in Icelandic children were similar to what has been seen in other studies, interesting differences were observed, such as a higher abundance of Blautia at an earlier age compared to other study populations. Higher alpha diversity in archaeal-positive samples, both in mothers and in children at the ages of 2 and 5, compared with archaeal-negative samples seen in the present study, is worth further investigation. Additionally, the study suggests a potential role of maternal and perinatal factors, particularly GDM, which was not evident until the age of 5 years, emphasizing the necessity of long-term studies.

The oral and gut microbiome develops from birth and plays important roles in health. This has been well studied in extremely preterm infants (EP; born <32 weeks gestation) and term infants (born >38 weeks gestation), but there is a paucity of research describing oral and gut microbiome development in late and moderate preterm infants (LMPT; 32 to 36 weeks gestation). Our study analyzed microbiome development in 160 LMPT infants from birth to 12 months corrected age. The results showed distinct microbial communities in stool and saliva, with increasing alpha diversity and niche specification over time. LMPT infants’ gut microbiome became dominated by Bifidobacterium by month 3, while the oral community was consistently dominated by Streptococcus . These results highlight that LMPT infants have gut and oral microbiome development that is more like term infants than EP infants, which has important implications for the care of LMPT infants.