Explore the vast range of titles available.

The phytotoxin coronatine (COR) promotes various aspects of Pseudomonas syringae virulence, including invasion through stomata, growth in the apoplast, and induction of disease symptoms. COR is a structural mimic of active jasmonic acid (JA) conjugates. Known activities of COR are mediated through its binding to the F-box—containing JA coreceptor CORONATINE INSENSITIVE1. By analyzing the interaction of P. syringae mutants with Arabidopsis thaliana mutants, we demonstrate that, in the apoplastic space of Arabidopsis, COR is a multifunctional defense suppressor. COR and the critical P. syringae type III effector HopM1 target distinct signaling steps to suppress callose deposition. In addition to its well-documented ability to suppress salicylic acid (SA) signaling, COR suppresses an SA-independent pathway contributing to callose deposition by reducing accumulation of an indole glucosinolate upstream of the activity of the PEN2 myrosinase. COR also suppresses callose deposition and promotes bacterial growth in coi1 mutant plants, indicating that COR may have multiple targets inside plant cells.

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger , the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger , which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides -encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H ₂S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage’s substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H ₂-producing Actinobacterium, Collinsella aerofaciens . Our findings provide genetic and metabolic details of how this H ₂-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.

Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.

How much does the microbiota influence the host's phenotype? Ridaura et al. ( 1241214 ; see the Perspective by Walker and Parkhill ) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota. Mice carrying gut bacteria from lean humans protect their cage mates from the effects of gut bacteria from fat humans. [Also see Perspective by Walker and Parkhill ] The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin’s microbiota (Ob) with mice containing the lean co-twin’s microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in over-coming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting. To characterize interactions among the gut microbiota, human milk oligosaccharides (HMOs), and osteoclast and osteoblast biology, young germ-free mice were colonized with cultured bacterial strains from a 6-mo-old stunted infant and fed a diet mimicking that consumed by the donor population. Adding purified bovine sialylated milk oligosaccharides (S-BMO) with structures similar to those in human milk to this diet increased femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses. Comparisons of germ-free and colonized mice revealed S-BMO-dependent and microbiota-dependent increases in cecal levels of succinate, increased numbers of small intestinal tuft cells, and evidence for activation of a succinate-induced tuft cell signaling pathway linked to Th2 immune responses. A prominent fucosylated HMO, 2′-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects. These results underscore the need to further characterize the balance between, and determinants of, osteoclastic and osteoblastic activity in stunted infants/children, and suggest that certain milk oligosaccharides may have therapeutic utility in this setting.

Significance Dietary fibers contain complex mixtures of biomolecules, making it difficult to develop/test hypotheses about how different fiber-types impact different components of the human gut microbiome and how microbiome changes that they produce are linked to human physiology. Here, we analyze microbiome and plasma proteome responses to consumption of two fiber-enriched snacks in two human studies. We use a variety of computational methods to correlate their effects on gut microbiome genes encoding enzymes that degrade complex fiber-associated polysaccharides, the microbial products of polysaccharide degradation, and plasma proteins representing diverse physiological processes. This approach can be used to guide the design of fiber-containing snacks that more precisely manipulate microbiome features in ways that improve nutritional and health status.

The gut microbiota influences numerous aspects of human biology. One facet that has not been thoroughly explored is its impact on the host proteome. We hypothesized that the microbiota may produce certain of its effects through covalent modification of host proteins. We focused on protein lysine ε-acetylation because of its recently discovered roles in regulation of cell metabolism, and the potential for products of microbial fermentation to interact with the lysine acetylation machinery of host cells. Germ-free mice, fed a ¹⁵N-labeled diet for two generations, were colonized as adults with a microbiota harvested from conventionally raised mouse donors. Using high-resolution mass spectrometry, we quantified 3,891 liver and proximal colonic proteins, 558 of which contained 1,602 sites of lysine acetylation, 43% not previously described. Multiple proteins from multiple subcellular compartments underwent microbiota-associated increases in their levels of lysine acetylation at one or more residues, in one or both tissues. Acetylated proteins were enriched in functions related to energy production, respiration, and primary metabolism. A number of the acetylation events affect lysine residues at or near the active sites of enzymes, whereas others occur at locations that may affect other facets of protein function. One of these modifications, affecting Lys292 in mouse α-1-antitrypsin, was detected in the corresponding lysine of the human serum protein. Methods described in this report can be applied to other co- or posttranslational modifications, and add quantitation of protein expression and covalent modification to the arsenal of techniques for characterizing the dynamic, important interactions between gut symbionts and their hosts.

Background Terpenes are one of the most diverse and abundant classes of natural biomolecules, collectively enabling a variety of therapeutic, energy, and cosmetic applications. Recent genomics investigations have predicted a large untapped reservoir of bacterial terpene synthases residing in the genomes of uncultivated organisms living in the soil, indicating a vast array of putative terpenoids waiting to be discovered. Results We aimed to develop a high-throughput functional metagenomic screening system for identifying novel terpene synthases from bacterial metagenomes by relieving the toxicity of terpene biosynthesis precursors to the Escherichia coli host. The precursor toxicity was achieved using an inducible operon encoding the prenyl pyrophosphate synthetic pathway and supplementation of the mevalonate precursor. Host strain and screening procedures were finely optimized to minimize false positives arising from spontaneous mutations, which avoid the precursor toxicity. Our functional metagenomic screening of human fecal metagenomes yielded a novel β-farnesene synthase, which does not show amino acid sequence similarity to known β-farnesene synthases. Engineered S. cerevisiae expressing the screened β-farnesene synthase produced 120 mg/L β-farnesene from glucose (2.86 mg/g glucose) with a productivity of 0.721 g/L∙h. Conclusions A unique functional metagenomic screening procedure was established for screening terpene synthases from metagenomic libraries. This research proves the potential of functional metagenomics as a sequence-independent avenue for isolating targeted enzymes from uncultivated organisms in various environmental habitats.

The human gut microbiota is hugely diverse, with many strain variants having a multiplicity of effects on host metabolism and immunity. To define some of these functions, Wu et al. made libraries of mutants of Bacteroides species known for their capacity to process otherwise intractable dietary fiber. Germ-free mice colonized with defined gut microbiota communities containing the mutants were fed specific diets containing different ratios of fat and fiber. Genes, strains, and species were identified that were associated with specific metabolic pathways. The community responses to dietary shifts were manipulated in an attempt to characterize species for their probiotic or therapeutic potential. Science , this issue 10.1126/science.aac5992 > To design probiotics, gut microbe fitness determinants and niches were characterized and responses to dietary changes monitored. Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness.

Changing food preferences brought about by westernization that have deleterious health effects 1 , 2 —combined with myriad forces that are contributing to increased food insecurity—are catalysing efforts to identify more nutritious and affordable foods 3 . Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity 4 – 6 . A substantial number of reports have explored the effects of dietary fibre on the gut microbial community 7 – 9 . However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state. Fibre snacks that target distinct features of the microbiomes of donors with obesity transplanted into gnotobiotic mice also lead to fibre-specific changes in the microbiome and physiology when used in controlled-diet human studies.