Reconstructing genome history is complex but necessary to reveal quantitative principles governing genome evolution. Such reconstruction requires recapitulating into a single evolutionary framework the evolution of genome architecture and gene repertoire. Here, we reconstructed the genome history of the genus Lachancea that appeared to cover a continuous evolutionary range from closely related to more diverged yeast species. Our approach integrated the generation of a high-quality genome data set; the development of AnChro, a new algorithm for reconstructing ancestral genome architecture; and a comprehensive analysis of gene repertoire evolution. We found that the ancestral genome of the genus Lachancea contained eight chromosomes and about 5173 protein-coding genes. Moreover, we characterized 24 horizontal gene transfers and 159 putative gene creation events that punctuated species diversification. We retraced all chromosomal rearrangements, including gene losses, gene duplications, chromosomal inversions and translocations at single gene resolution. Gene duplications outnumbered losses and balanced rearrangements with 1503, 929, and 423 events, respectively. Gene content variations between extant species are mainly driven by differential gene losses, while gene duplications remained globally constant in all lineages. Remarkably, we discovered that balanced chromosomal rearrangements could be responsible for up to 14% of all gene losses by disrupting genes at their breakpoints. Finally, we found that nonsynonymous substitutions reached fixation at a coordinated pace with chromosomal inversions, translocations, and duplications, but not deletions. Overall, we provide a granular view of genome evolution within an entire eukaryotic genus, linking gene content, chromosome rearrangements, and protein divergence into a single evolutionary framework.

Lifestyle factors, such as diet, strongly influence the structure, diversity, and composition of the microbiome. While we have witnessed over the last several years a resurgence of interest in fermented foods, no study has specifically explored the effects of their consumption on gut microbiota in large cohorts. To assess whether the consumption of fermented foods is associated with a systematic signal in the gut microbiome and metabolome, we used a multi-omic approach (16S rRNA amplicon sequencing, metagenomic sequencing, and untargeted mass spectrometry) to analyze stool samples from 6,811 individuals from the American Gut Project, including 115 individuals specifically recruited for their frequency of fermented food consumption for a targeted 4-week longitudinal study. We observed subtle but statistically significant differences between consumers and nonconsumers in beta diversity as well as differential taxa between the two groups. We found that the metabolome of fermented food consumers was enriched with conjugated linoleic acid (CLA), a putatively health-promoting molecule. Cross-omic analyses between metagenomic sequencing and mass spectrometry suggest that CLA may be driven by taxa associated with fermented food consumers. Collectively, we found modest yet persistent signatures associated with fermented food consumption that appear present in multiple -omic types which motivate further investigation of how different types of fermented food impact the gut microbiome and overall health. IMPORTANCE Public interest in the effects of fermented food on the human gut microbiome is high, but limited studies have explored the association between fermented food consumption and the gut microbiome in large cohorts. Here, we used a combination of omics-based analyses to study the relationship between the microbiome and fermented food consumption in thousands of people using both cross-sectional and longitudinal data. We found that fermented food consumers have subtle differences in their gut microbiota structure, which is enriched in conjugated linoleic acid, thought to be beneficial. The results suggest that further studies of specific kinds of fermented food and their impacts on the microbiome and health will be useful.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt’s health effects.

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Background The microbiome of the digestive tract exerts fundamental roles in host physiology. Extrinsic factors including lifestyle and diet are widely recognized as key drivers of gut and oral microbiome compositions. Although drinking water is among the food items consumed in the largest amount, little is known about its potential impact on the microbiome. Objectives We explored the associations of plain drinking water source and intake with gut and oral microbiota compositions in a population-based cohort. Methods Microbiota, health, lifestyle, and food intake data were extracted from the American Gut Project public database. Associations of drinking water source (bottled, tap, filtered, or well water) and intake with global microbiota composition were evaluated using linear and logistic models adjusted for anthropometric, diet, and lifestyle factors in 3413 and 3794 individuals, respectively (fecal samples; 56% female, median [IQR] age: 48 [36–59] y; median [IQR] BMI: 23.3 [20.9–26.3] kg/m2), and in 283 and 309 individuals, respectively (oral samples). Results Drinking water source ranked among the key contributing factors explaining the gut microbiota variation, accounting for 13% [Faith's phylogenetic diversity (Faith's PD)] and 47% (Bray–Curtis dissimilarity) of the age effect size. Drinking water source was associated with differences in gut microbiota signatures, as revealed by β diversity analyses (P < 0.05; Bray–Curtis dissimilarity, weighted UniFrac distance). Subjects drinking mostly well water had higher fecal α diversity (P < 0.05; Faith's PD, observed amplicon sequence variants), higher Dorea, and lower Bacteroides, Odoribacter, and Streptococcus than the other groups. Low water drinkers also exhibited gut microbiota differences compared with high water drinkers (P < 0.05; Bray–Curtis dissimilarity, unweighted UniFrac distance) and a higher abundance of Campylobacter. No associations were found between oral microbiota composition and drinking water consumption. Conclusions Our results indicate that drinking water may be an important factor in shaping the human gut microbiome and that integrating drinking water source and intake as covariates in future microbiome analyses is warranted.

BACKGROUNDHelicobacter pylori (Hp) eradication therapy can alter gut microbiota, provoking gastro-intestinal (GI) symptoms that can be improved by probiotics. The effect on Hp patients of a Test fermented milk containing yogurt and three Lacticaseibacillus (L. paracasei CNCM I-1518, CNCM I-3689, L. rhamnosus CNCM I-3690) strains was assessed on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota composition and metabolites. In this aim, a randomized, double-blind, controlled trial was performed in 136 adults under Hp-treatment (14-day amoxicillin, clarithromycin, pantoprazole), who consumed the Test or a Control product for 28 days. Feces were analysed for gut microbiota composition, short chain fatty acids (SCFA), calprotectin, and viability of ingested strains.RESULTSNo effect of Test product was observed on AAD occurrence or duration, rating scores or number of days of GI symptoms. Hp-treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and of calprotectin, and a decrease of SCFA concentration. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj=0.02), Escherichia-Shigella (padj=0.0082) and Klebsiella (padj= 0.013) were significantly less abundant, and concentrations of major SCFA (p=0.035) and valerate (p = 0.045) were higher. Viable Lp and Lr strains from the Test product were mainly detected during product consumption in feces.CONCLUSIONSThe study showed that 14-day Hp triple therapy alters gut bacterial and fungal community, their metabolites and gut inflammatory markers. Consumption of a multi-strain fermented milk can induce faster recovery of the microbiota composition and SCFA production and limit the bloom of pathobionts. (ClinicalTrials.gov, NCT02900196; First Posted : September 14, 2016; https://www.clinicaltrials.gov/ct2/show/NCT02900196).

Objectives Fermented foods have gained much attention due to their proposed gut health benefits from recent clinical trials. However, very few studies have explored the effects of fermented foods, especially of plant origin, on gut microbiota composition and functional capacity in large human cohorts. Thus, the objective of this study was to assess whether self-reported fermented plant food consumption is associated with compositional or functional microbiome changes in a subset of individuals in the American Gut Project (AGP) cohort. Methods Using a multi-omics approach (e.g., 16S rRNA amplicon sequencing, metagenomic sequencing, and untargeted mass spectrometry), we analyzed stool samples from 6811 healthy individuals from the AGP including 115 individuals specifically recruited for their fermented plant food consumption for a targeted four-week longitudinal study. Results We observed subtle, yet statistically significant differences between fermented plant food consumers and non-consumers in beta diversity as well as differential taxa between the two groups. We found that the metabolome of fermented plant food consumers was enriched with conjugated linoleic acid (CLA), a putatively health-promoting compound. Cross-omic analyses between metagenomic sequencing and mass spectrometry suggest that CLA may be driven by taxa associated with fermented plant food consumers. Conclusions Collectively, we found modest, yet persistent signatures associated with fermented plant food consumption that appear present in multiple omic types, which motivates further investigation of how different types of fermented foods may impact the human gut microbiome and overall health. Funding Sources Danone Nutricia Research.