Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.

Terniopsisyongtaiensis (Podostemaceae), a new species from South East China based on morphological and genomic data.

The new species Terniopsisyongtaiensis X.X. Su, Miao Zhang & Bing-Hua Chen, from Fujian Province, China, is described and illustrated. It is similar to T.heterostaminata from Thailand, but differs in its two fertile stamens, fewer but longer vegetative ramuli, fewer but shorter flowering ramuli, shorter pedicels, capsule-stalk and stamens. The complete chroloplast genome of the new species is 129,074 bp long and has a typical quadripartite structure, including two inverted repeat regions (IRs) of 18,504 bp in length, separated by a large single-copy (LSC) and a small single-copy (SSC) regions of 79,000 bp and 13,066 bp, respectively. The ycf1 and ycf2 genes were lost compared to most higher plants, leading to a substantial reduction in the IR. The phylogenetic analysis using both matK and nrITS revealed that T.yongtaiensis is sister to T.heterostaminata with moderate support, and formed a clade with other Terniopsis species, suggesting that the new species belongs to Tristichoideae.

Danxiaorchismangdangshanensis (Orchidaceae, Epidendroideae), a new species from central Fujian Province based on morphological and genomic data.

Danxiaorchismangdangshanensis, a new mycoheterotrophic species from Fujian Province, China, is described and illustrated. The new species is morphologically similar to D.singchiana, but its callus of labellum is a less distinctive Y-shape with three auricles on the apex, four pollinia that are narrowly elliptic in shape and equal in size, and it lacks fine roots. The plastome of D.mangdangshanensis is highly degraded. Phylogenetic analyses distinguished D.mangdangshanensis from its congeners, D.singchiana and D.yangii, with strong support based on nrITS + matK and plastomes, respectively.

Polypleurumchinense (Podostemaceae), a new species from Fujian, China, based on morphological and genomic evidence.

We describe Polypleurumchinense, a new species of Podostemaceae from Yunxiao County, Fujian Province, China, based on morphological and molecular data and the genus Polypleurum is recorded here for the first time from China. Polypleurumchinense has a gross morphology similar to P.longistylosum, but it can be distinguished from the latter by its narrower roots, more numerous and longer leaves, shorter stigmas and more numerous ovules per locule. To distinguish the new Polypleurum species and study its phylogenetic position, its complete plastome was sequenced and characterised. The plastome is 132,110 bp in length, including a pair of inverted repeat regions (IRs) of 20,389 bp divided by the large single-copy (LSC) and small single-copy (SSC) regions of 79,022 bp and 12,310 bp, respectively. The plastome size of P.chinense is relatively smaller compared to most angiosperms due to the absence of the ycf1 and ycf2 genes in the IR regions. The phylogenetic analyses also strongly support the separation of the new species from other taxa.

Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women.

BACKGROUND: Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community-dwelling healthy menopausal women. METHODS: Estimated SMM was derived from whole-body dual-energy X-ray absorptiometry. We performed integrated analyses on whole-genome sequencing, shotgun metagenomic sequencing, and serum short-chain fatty acids (SCFAs), as well as available host SMM measurements among community-dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome-wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one-sample and two-sample Mendelian randomization (MR) analyses, respectively. RESULTS: In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate-producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10-7 ) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10-4 ) and B. virosa (SCC = 0.17, P = 2.4 × 10-4 )]. One-sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two-sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). CONCLUSIONS: Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.

GCY-35/GCY-36-TAX-2/TAX-4 Signalling in O2 Sensory Neurons Mediates Acute Functional Ethanol Tolerance in Caenorhabditis elegans.

Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood. In Caenorhabditis elegans, NPR-1 negatively regulates the development of acute tolerance to ethanol. Here, using in vivo Ca2+ imaging, behavioural tests and chemogenetic manipulation, we show that the soluble guanylate cyclase complex GCY-35/GCY-36-TAX-2/TAX-4 signalling pathway in O2 sensory neurons positively regulates acute functional tolerance in npr-1 worms.

cGMP Signalling Mediates Water Sensation (Hydrosensation) and Hydrotaxis in Caenorhabditis elegans.

Animals have developed the ability to sense the water content in their habitats, including hygrosensation (sensing humidity in the air) and hydrosensation (sensing the water content in other microenvironments), and they display preferences for specific water contents that influence their mating, reproduction and geographic distribution. We developed and employed four quantitative behavioural test paradigms to investigate the molecular and cellular mechanisms underlying sensing the water content in an agar substrate (hydrosensation) and hydrotaxis in Caenorhabditis elegans. By combining a reverse genetic screen with genetic manipulation, optogenetic neuronal manipulation and in vivo Ca(2+) imaging, we demonstrate that adult worms avoid the wetter areas of agar plates and hypo-osmotic water droplets. We found that the cGMP signalling pathway in ciliated sensory neurons is involved in hydrosensation and hydrotaxis in Caenorhabditis elegans.

Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans.

Sensory modulation is essential for animal sensations, behaviours and survival. Peripheral modulations of nociceptive sensations and aversive behaviours are poorly understood. Here we identify a biased cross-inhibitory neural circuit between ASH and ASI sensory neurons. This inhibition is essential to drive normal adaptive avoidance of a CuSO4 (Cu(2+)) challenge in Caenorhabditis elegans. In the circuit, ASHs respond to Cu(2+) robustly and suppress ASIs via electro-synaptically exciting octopaminergic RIC interneurons, which release octopamine (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In addition, ASIs sense Cu(2+) and permit a rapid onset of Cu(2+)-evoked responses in Cu(2+)-sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation among sensory neurons via reciprocal inhibition fine-tunes the nociception and avoidance behaviour.