Functional host-specific adaptation of the intestinal microbiome in hominids.

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research.

Our understanding of how the gut microbiome interacts with its human host has been restrained by limited access to longitudinal datasets to examine stability and dynamics, and by having only a few isolates to test mechanistic hypotheses. Here, we present the Broad Institute-OpenBiome Microbiome Library (BIO-ML), a comprehensive collection of 7,758 gut bacterial isolates paired with 3,632 genome sequences and longitudinal multi-omics data. We show that microbial species maintain stable population sizes within and across humans and that commonly used 'omics' survey methods are more reliable when using averages over multiple days of sampling. Variation of gut metabolites within people over time is associated with amino acid levels, and differences across people are associated with differences in bile acids. Finally, we show that genomic diversification can be used to infer eco-evolutionary dynamics and in vivo selection pressures for strains within individuals. The BIO-ML is a unique resource designed to enable hypothesis-driven microbiome research.

Influence of tree shape and evolutionary time-scale on phylogenetic diversity metrics.

During the last decades, describing, analysing and understanding the phylogenetic structure of species assemblages has been a central theme in both community ecology and macro-ecology. Among the wide variety of phylogenetic structure metrics, three have been predominant in the literature: Faith's phylogenetic diversity (PDFaith), which represents the sum of the branch lengths of the phylogenetic tree linking all species of a particular assemblage, the mean pairwise distance between all species in an assemblage (MPD) and the pairwise distance between the closest relatives in an assemblage (MNTD). Comparisons between studies using one or several of these metrics are difficult because there has been no comprehensive evaluation of the phylogenetic properties each metric captures. In particular it is unknown how PDFaith relates to MDP and MNTD. Consequently, it is possible that apparently opposing patterns in different studies might simply reflect differences in metric properties. Here, we aim to fill this gap by comparing these metrics using simulations and empirical data. We first used simulation experiments to test the influence of community structure and size on the mismatch between metrics whilst varying the shape and size of the phylogenetic tree of the species pool. Second we investigated the mismatch between metrics for two empirical datasets (gut microbes and global carnivoran assemblages). We show that MNTD and PDFaith provide similar information on phylogenetic structure, and respond similarly to variation in species richness and assemblage structure. However, MPD demonstrate a very different behaviour, and is highly sensitive to deep branching structure. We suggest that by combining complementary metrics that are sensitive to processes operating at different phylogenetic depths (i.e. MPD and MNTD or PDFaith) we can obtain a better understanding of assemblage structure.

A branch-heterogeneous model of protein evolution for efficient inference of ancestral sequences.

Most models of nucleotide or amino acid substitution used in phylogenetic studies assume that the evolutionary process has been homogeneous across lineages and that composition of nucleotides or amino acids has remained the same throughout the tree. These oversimplified assumptions are refuted by the observation that compositional variability characterizes extant biological sequences. Branch-heterogeneous models of protein evolution that account for compositional variability have been developed, but are not yet in common use because of the large number of parameters required, leading to high computational costs and potential overparameterization. Here, we present a new branch-nonhomogeneous and nonstationary model of protein evolution that captures more accurately the high complexity of sequence evolution. This model, henceforth called Correspondence and likelihood analysis (COaLA), makes use of a correspondence analysis to reduce the number of parameters to be optimized through maximum likelihood, focusing on most of the compositional variation observed in the data. The model was thoroughly tested on both simulated and biological data sets to show its high performance in terms of data fitting and CPU time. COaLA efficiently estimates ancestral amino acid frequencies and sequences, making it relevant for studies aiming at reconstructing and resurrecting ancestral amino acid sequences. Finally, we applied COaLA on a concatenate of universal amino acid sequences to confirm previous results obtained with a nonhomogeneous Bayesian model regarding the early pattern of adaptation to optimal growth temperature, supporting the mesophilic nature of the Last Universal Common Ancestor.

[Treatment of amenorrhea-galactorrhea with bromo-ergocryptine. Apropos of 12 cases]. / Traitement de l'aménorrhée-galactorrhée par la bromo-ergocryptine. A propos de 12 cas.

The authors report the action of bromergocryptine in 12 patients who were suffering from a syndrome of amenorrhoea with galactorrhoea and hyperprolactinism. None of these 12 patients had a pituitary tumour; or else they had been operated on before treatment. Only in one case was the syndrome linked to taking oral contraceptives, which had been stopped more than six months previously. The dose of bromergocryptine was 5 mg. a day. If this dose fails it is possible to raise it after two months' observation. The galactorrhoea disappeared or markedly decreased in 8 out of the 12 cases. Ovulatory cycles started in 9 out of the 12. 5 of the women wanted a pregnancy: 4 succeeded and 2 of them have already been delivered of normal children. Bromergocryptine (CB 154) has thus proved itself to be remarkably effective in hyperprolactinism, not caused by a pituitary tumour, which gives rise to amenorrhoea and galactorrhoea. All the same, its long-term use, especially after stopping treatment, is still to be evaluated.

[Virilizing tumours of the adrenal cortex with unimpaired menstruation (author's transl)]. / Tumeurs virilisantes cortico-surrénaliennes sans anomalies de la menstruation.

Virilizing adenomas of the adrenal cortex entail, typically, hirsutism, amenorrhea and hypertrophy of the clitoris. We report two cases of adrenal adenoma, both revealed by hirsutism and significant biological features, but both without any alteration of the menstrual cycle. One of our 2 patients showed moderate hypertrophy of the clitoris. In the first patient, the tumour has been located thanks to dexamethasone--modifiying adrenal secretion, and in the second patient, thanks to angiography. These two cases reported are a warning never to neglect more hirsutism, even, when unobstrusive, and always to undertake minimal hormonal investigations.