The impact of the gut microbiota on human health: an integrative view.

The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota--bacteria, viruses, and eukaryotes--have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota.

Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models.

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

Manipulation of the seagrass-associated microbiome reduces disease severity.

Host-associated microbes influence host health and function and can be a first line of defence against infections. While research increasingly shows that terrestrial plant microbiomes contribute to bacterial, fungal, and oomycete disease resistance, no comparable experimental work has investigated marine plant microbiomes or more diverse disease agents. We test the hypothesis that the eelgrass (Zostera marina) leaf microbiome increases resistance to seagrass wasting disease. From field eelgrass with paired diseased and asymptomatic tissue, 16S rRNA gene amplicon sequencing revealed that bacterial composition and richness varied markedly between diseased and asymptomatic tissue in one of the two years. This suggests that the influence of disease on eelgrass microbial communities may vary with environmental conditions. We next experimentally reduced the eelgrass microbiome with antibiotics and bleach, then inoculated plants with Labyrinthula zosterae, the causative agent of wasting disease. We detected significantly higher disease severity in eelgrass with a native microbiome than an experimentally reduced microbiome. Our results over multiple experiments do not support a protective role of the eelgrass microbiome against L. zosterae. Further studies of these marine host-microbe-pathogen relationships may continue to show new relationships between plant microbiomes and diseases.

Transmission mode and dispersal traits correlate with host specificity in mammalian gut microbes.

Different host species associate with distinct gut microbes in mammals, a pattern sometimes referred to as phylosymbiosis. However, the processes shaping this host specificity are not well understood. One model proposes that barriers to microbial transmission promote specificity by limiting microbial dispersal between hosts. This model predicts that specificity levels measured across microbes is correlated to transmission mode (vertical vs. horizontal) and individual dispersal traits. Here, we leverage two large publicly available gut microbiota data sets (1490 samples from 195 host species) to test this prediction. We found that host specificity varies widely across bacteria (i.e., there are generalist and specialist bacteria) and depends on transmission mode and dispersal ability. Horizontally-like transmitted bacteria equipped with traits that facilitate switches between host (e.g., tolerance to oxygen) were found to be less specific (more generalist) than microbes without those traits, for example, vertically-like inherited bacteria that are intolerant to oxygen. Altogether, our findings are compatible with a model in which limited microbial dispersal abilities foster host specificity.

Response to "Vast (but avoidable) underestimation of global biodiversity".

This Formal Comment provides clarifications on the authors' recent estimates of global bacterial diversity and the current status of the field, and responds to a Formal Comment from John Wiens regarding their prior work.

Nitrogen Fixation and Microbial Communities Associated with Decomposing Seagrass Leaves in Temperate Coastal Waters.

Seagrass meadows play pivotal roles in coastal biochemical cycles, with nitrogen fixation being a well-established process associated with living seagrass. Here, we tested the hypothesis that nitrogen fixation is also associated with seagrass debris in Danish coastal waters. We conducted a 52-day in situ experiment to investigate nitrogen fixation (proxied by acetylene reduction) and dynamics of the microbial community (16S rRNA gene amplicon sequencing) and the nitrogen fixing community (nifH DNA/RNA amplicon sequencing) associated with decomposing Zostera marina leaves. The leaves harboured distinct microbial communities, including distinct nitrogen fixers, relative to the surrounding seawater and sediment throughout the experiment. Nitrogen fixation rates were measurable on most days, but highest on days 3 (dark, 334.8 nmol N g-1 dw h-1) and 15 (light, 194.6 nmol N g-1 dw h-1). Nitrogen fixation rates were not correlated with the concentration of inorganic nutrients in the surrounding seawater or with carbon:nitrogen ratios in the leaves. The composition of nitrogen fixers shifted from cyanobacterial Sphaerospermopsis to heterotrophic genera like Desulfopila over the decomposition period. On the days with highest fixation, nifH RNA gene transcripts were mainly accounted for by cyanobacteria, in particular by Sphaerospermopsis and an unknown taxon (order Nostocales), alongside Proteobacteria. Our study shows that seagrass debris in temperate coastal waters harbours substantial nitrogen fixation carried out by cyanobacteria and heterotrophic bacteria that are distinct relative to the surrounding seawater and sediments. This suggests that seagrass debris constitutes a selective environment where degradation is affected by the import of nitrogen via nitrogen fixation.

Successional dynamics of the cultivated kelp microbiome.

Kelp are important primary producers that are colonized by diverse microbes that can have both positive and negative effects on their hosts. The kelp microbiome could support the burgeoning kelp cultivation sector by improving host growth, stress tolerance, and resistance to disease. Fundamental questions about the cultivated kelp microbiome still need to be addressed before microbiome-based approaches can be developed. A critical knowledge gap is how cultivated kelp microbiomes change as hosts grow, particularly following outplanting to sites that vary in abiotic conditions and microbial source pools. In this study we assessed if microbes that colonize kelp in the nursery stage persist after outplanting. We characterized microbiome succession over time on two species of kelp, Alaria marginata and Saccharina latissima, outplanted to open ocean cultivation sites in multiple geographic locations. We tested for host-species specificity of the microbiome and the effect of different abiotic conditions and microbial source pools on kelp microbiome stability during the cultivation process. We found the microbiome of kelp in the nursery is distinct from that of outplanted kelp. Few bacteria persisted on kelp following outplanting. Instead, we identified significant microbiome differences correlated with host species and microbial source pools at each cultivation site. Microbiome variation related to sampling month also indicates that seasonality in host and/or abiotic factors may influence temporal succession and microbiome turnover in cultivated kelps. This study provides a baseline understanding of microbiome dynamics during kelp cultivation and highlights research needs for applying microbiome manipulation to kelp cultivation.

Seagrass (Zostera marina) transplant experiment reveals core microbiota and resistance to environmental change.

Zostera marina (seagrass) is a coastal marine angiosperm that sustains a diverse and productive ecosystem. Seagrass-associated microbiota support host health, yet the ecological processes that maintain biodiversity and stability of the seagrass leaf microbiota are poorly understood. We tested two hypotheses: (1) Microbes select seagrass leaves as habitat such that they consistently host distinct microbiota and/or core taxa in comparison to nearby substrates, and (2) seagrass leaf microbiota are stable once established and are resistant to change when transplanted to a novel environment. We reciprocally transplanted replicate seagrass shoots (natural and surface sterilized/dead tissue treatments) among four meadows with different environmental conditions and deployed artificial seagrass treatments in all four meadows. At the end of the 5-day experiment, the established microbiota on natural seagrass partially turned over to resemble microbial communities in the novel meadow, and all experimental treatments hosted distinct surface microbiota. We consistently found that natural and sterilized/dead seagrass hosted more methanol-utilizing bacteria compared to artificial seagrass and water, suggesting that seagrass core microbiota are shaped by taxa that metabolize seagrass exudates coupled with minor roles for host microbial defence and/or host-directed recruitment. We found evidence that the local environment strongly influenced the seagrass leaf microbiota in natural meadows and that transplant location explained more variation than experimental treatment. Transplanting resulted in high turnover and variability of the seagrass leaf microbiota, suggesting that it is flexibly assembled in a wide array of environmental conditions which may contribute to resilience of seagrass in future climate change scenarios.

A census-based estimate of Earth's bacterial and archaeal diversity.

The global diversity of Bacteria and Archaea, the most ancient and most widespread forms of life on Earth, is a subject of intense controversy. This controversy stems largely from the fact that existing estimates are entirely based on theoretical models or extrapolations from small and biased data sets. Here, in an attempt to census the bulk of Earth's bacterial and archaeal ("prokaryotic") clades and to estimate their overall global richness, we analyzed over 1.7 billion 16S ribosomal RNA amplicon sequences in the V4 hypervariable region obtained from 492 studies worldwide, covering a multitude of environments and using multiple alternative primers. From this data set, we recovered 739,880 prokaryotic operational taxonomic units (OTUs, 16S-V4 gene clusters at 97% similarity), a commonly used measure of microbial richness. Using several statistical approaches, we estimate that there exist globally about 0.8-1.6 million prokaryotic OTUs, of which we recovered somewhere between 47%-96%, representing >99.98% of prokaryotic cells. Consistent with this conclusion, our data set independently "recaptured" 91%-93% of 16S sequences from multiple previous global surveys, including PCR-independent metagenomic surveys. The distribution of relative OTU abundances is consistent with a log-normal model commonly observed in larger organisms; the total number of OTUs predicted by this model is also consistent with our global richness estimates. By combining our estimates with the ratio of full-length versus partial-length (V4) sequence diversity in the SILVA sequence database, we further estimate that there exist about 2.2-4.3 million full-length OTUs worldwide. When restricting our analysis to the Americas, while controlling for the number of studies, we obtain similar richness estimates as for the global data set, suggesting that most OTUs are globally distributed. Qualitatively similar results are also obtained for other 16S similarity thresholds (90%, 95%, and 99%). Our estimates constrain the extent of a poorly quantified rare microbial biosphere and refute recent predictions that there exist trillions of prokaryotic OTUs.

Evidence for long-lasting alterations in the fecal microbiota following prenatal alcohol exposure.

BACKGROUND: There is growing evidence that the gut microbiota can be shaped by early-life experiences/exposures, with long-term consequences for brain, behavior, and health. Changes in the gut microbiota have also been identified in neurodevelopmental disorders including Autism Spectrum Disorder and schizophrenia. In contrast, no studies to date have investigated whether the gut microbiota is altered in individuals with Fetal Alcohol Spectrum Disorder (FASD), the neurodevelopmental disorder that results from prenatal alcohol exposure (PAE). The current study was designed to assess the impact of PAE on the fecal microbiota. METHODS: We used a rodent model in which pregnant Sprague-Dawley rats were provided with an EtOH-containing diet or a control diet throughout gestation. Fecal samples were collected from adult male and female animals and 16s rRNA sequencing was performed. RESULTS: Overall, PAE rats showed greater richness of bacterial species, with community structure investigations demonstrating distinct clustering by prenatal treatment. In addition, prenatal treatment and sex-specific alterations were observed for many specific microbes. For example, in males, Bacteroides and Bifidobacterium, and in females, Faecalitalea and Proteus, differed in abundance between PAE and control rats. CONCLUSIONS: Taken together, these results show for the first time that PAE has a long-lasting and sex-specific impact on the fecal microbiota. Further research is needed that considers fetal microbiota in the development of new interventions in FASD.

The microbiota of intertidal macroalgae Fucus distichus is site-specific and resistant to change following transplant.

It is unclear how host-associated microbial communities will be affected by future environmental change. Characterizing how microbiota differ across sites with varying environmental conditions and assessing the stability of the microbiota in response to abiotic variation are critical steps towards predicting outcomes of environmental change. Intertidal organisms are valuable study systems because they experience extreme variation in environmental conditions on tractable timescales such as tide cycles and across small spatial gradients in the intertidal zone. Here we show a widespread intertidal macroalgae, Fucus distichus, hosts site-specific microbiota over small (meters to kilometres) spatial scales. We demonstrate stability of site-specific microbial associations by manipulating the host environment and microbial species pool with common garden and reciprocal transplant experiments. We hypothesized that F. distichus microbiota would readily shift to reflect the contemporary environment due to selective filtering by abiotic conditions and/or colonization by microbes from the new environment or nearby hosts. Instead, F. distichus microbiota was stable for days after transplantation in both the laboratory and field. Our findings expand the current understanding of microbiota dynamics on an intertidal foundation species. These results may also point to adaptations for withstanding short-term environmental variation, in hosts and/or microbes, facilitating stable host-microbial associations.

EukRef: Phylogenetic curation of ribosomal RNA to enhance understanding of eukaryotic diversity and distribution.

Environmental sequencing has greatly expanded our knowledge of micro-eukaryotic diversity and ecology by revealing previously unknown lineages and their distribution. However, the value of these data is critically dependent on the quality of the reference databases used to assign an identity to environmental sequences. Existing databases contain errors and struggle to keep pace with rapidly changing eukaryotic taxonomy, the influx of novel diversity, and computational challenges related to assembling the high-quality alignments and trees needed for accurate characterization of lineage diversity. EukRef (eukref.org) is an ongoing community-driven initiative that addresses these challenges by bringing together taxonomists with expertise spanning the eukaryotic tree of life and microbial ecologists, who use environmental sequence data to develop reliable reference databases across the diversity of microbial eukaryotes. EukRef organizes and facilitates rigorous mining and annotation of sequence data by providing protocols, guidelines, and tools. The EukRef pipeline and tools allow users interested in a particular group of microbial eukaryotes to retrieve all sequences belonging to that group from International Nucleotide Sequence Database Collaboration (INSDC) (GenBank, the European Nucleotide Archive [ENA], or the DNA DataBank of Japan [DDBJ]), to place those sequences in a phylogenetic tree, and to curate taxonomic and environmental information for the group. We provide guidelines to facilitate the process and to standardize taxonomic annotations. The final outputs of this process are (1) a reference tree and alignment, (2) a reference sequence database, including taxonomic and environmental information, and (3) a list of putative chimeras and other artifactual sequences. These products will be useful for the broad community as they become publicly available (at eukref.org) and are shared with existing reference databases.

Microeukaryotic Communities Associated With the Seagrass Zostera marina Are Spatially Structured.

Epibiotic microorganisms link seagrass productivity to higher trophic levels, but little is known about the processes structuring these communities, and which taxa consistently associate with seagrass. We investigated epibiotic microeukaryotes on seagrass (Zostera marina) leaves, substrates, and planktonic microeukaryotes in ten meadows in the Northeast Pacific. Seagrass epibiotic communities are distinct from planktonic and substrate communities. We found sixteen core microeukaryotes, including dinoflagellates, diatoms, and saprotrophic stramenopiles. Some likely use seagrass leaves as a substrate, others for grazing, or they may be saprotrophic organisms involved in seagrass decomposition or parasites; their relatives have been previously reported from marine sediments and in association with other hosts such as seaweeds. Core microeukaryotes were spatially structured, and none were ubiquitous across meadows. Seagrass epibiota were more spatially structured than planktonic communities, mostly due to spatial distance and changes in abiotic conditions across space. Seawater communities were relatively more similar in composition across sites and more influenced by the environmental component, but more variable over time. Core and transient taxa were both mostly structured by spatial distance and the abiotic environment, with little effect of host attributes, further indicating that those core taxa would not show a strong specific association with Z. marina.

Kelp-associated Microbiota are Structured by Host Anatomy1.

Seaweed-associated microbiota are essential for the health and resilience of nearshore ecosystems, marine biogeochemical cycling, and host health. Yet much remains unknown about the ecology of seaweed-microbe symbioses. In this study, we quantified fine-scale patterns of microbial community structure across distinct anatomical regions of the kelp Laminaria setchellii. These anatomical regions represent a gradient of tissue ages: perennial holdfasts can be several years old, whereas stipe epicortex and blades are younger annual structures. Within blades, new growth occurs at the base, while the blade tips may be several months old and undergoing senescence. We hypothesized that microbial communities will differ across anatomical regions (holdfast, stipe, blade base, and blade tip), such that younger tissues will harbor fewer microbes that are more consistent across replicate individuals. Our data support this hypothesis, with the composition of bacterial (16S rRNA gene) and microeukaryote (18S rRNA gene) communities showing significant differences across the four anatomical regions, with the surfaces of older tissues (holdfast and blade tips) harboring significantly greater microbial richness compared to the younger tissues of the meristematic region. Additional samples collected from the surfaces of new L. setchellii recruits (<1y old) also showed differences in microbial community structure across anatomical regions, which demonstrates that these microbial differences are established early. We also observed this pattern in two additional algal species, suggesting that microbial community structure across host anatomy may be a common feature of the seaweed microbiome.

Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa.

Linear growth delay (stunting) affects roughly 155 million children under the age of 5 years worldwide. Treatment has been limited by a lack of understanding of the underlying pathophysiological mechanisms. Stunting is most likely associated with changes in the microbial community of the small intestine, a compartment vital for digestion and nutrient absorption. Efforts to better understand the pathophysiology have been hampered by difficulty of access to small intestinal fluids. Here, we describe the microbial community found in the upper gastrointestinal tract of stunted children aged 2-5 y living in sub-Saharan Africa. We studied 46 duodenal and 57 gastric samples from stunted children, as well as 404 fecal samples from stunted and nonstunted children living in Bangui, Central African Republic, and in Antananarivo, Madagascar, using 16S Illumina Amplicon sequencing and semiquantitative culture methods. The vast majority of the stunted children showed small intestinal bacterial overgrowth dominated by bacteria that normally reside in the oropharyngeal cavity. There was an overrepresentation of oral bacteria in fecal samples of stunted children, opening the way for developing noninvasive diagnostic markers. In addition, Escherichia coli/Shigella sp. and Campylobacter sp. were found to be more prevalent in stunted children, while Clostridia, well-known butyrate producers, were reduced. Our data suggest that stunting is associated with a microbiome "decompartmentalization" of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.

Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting.

BACKGROUND: Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. OBJECTIVE: We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. METHODS: We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. RESULTS: As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. CONCLUSIONS: Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

Sympatric kelp species share a large portion of their surface bacterial communities.

Kelp forest ecosystems are biodiversity hotspots, providing habitat for dense assemblages of marine organisms and nutrients for marine and terrestrial food webs. The surfaces of kelps support diverse microbial communities that facilitate the transfer of carbon from algal primary production to higher trophic levels. We quantified the diversity of bacteria on the surfaces of eight sympatric kelp species from four sites in British Columbia. Kelp-associated bacterial communities are significantly different from their environment, even though 86% of their bacterial taxa are shared with seawater and 97% are shared with rocky substrate. This differentiation is driven by differences in relative abundance of the bacterial taxa present. Similarly, a large portion of bacterial taxa (37%) is shared among all eight kelp species, yet differential abundance of bacterial taxa underlies differences in community structure among species. Kelp-associated bacterial diversity does not track host phylogeny; instead bacterial community composition is correlated with the life-history strategy of the host, with annual and perennial kelps supporting divergent bacterial communities. These data provide the first community-scale investigation of kelp forest-associated bacterial diversity. More broadly, this study provides insight into mechanisms that may structure bacterial communities among closely related sympatric host species.

Incubation with macroalgae induces large shifts in water column microbiota, but minor changes to the epibiota of co-occurring macroalgae.

Macroalgae variably promote and deter microbial growth through release of organic carbon and antimicrobial compounds into the water column. Consequently, macroalgae influence the microbial composition of the surrounding water column and biofilms on nearby surfaces. Here, we use manipulative experiments to test the hypotheses that (i) Nereocystis luetkeana and Mastocarpus sp. macroalgae alter the water column microbiota in species-specific manner, that (ii) neighbouring macroalgae alter the bacterial communities on the surface (epibiota) of actively growing Nereocystis luetkeana meristem fragments (NMFs), and that (iii) neighbours alter NMF growth rate. We also assess the impact of laboratory incubation on macroalgal epibiota by comparing each species to wild counterparts. We find strong differences between the Nereocystis and Mastocarpus epibiota that are maintained in the laboratory. Nereocystis and Mastocarpus alter water column bacterial community composition and richness in a species specific manner, but cause only small compositional shifts on NMF surfaces that do not differ by species, and do not change richness. Co-incubation with macroalgae results in significant change in abundance of fivefold more genera in the water column compared to NMF surfaces, although the direction (i.e., enrichment or reduction) of shift is generally consistent between the water and NMF surfaces. Finally, NMFs grew during the experiment, but growth did not depend on the presence or identity of neighbouring macroalgae. Thus, macroalgae exhibit a strong and species-specific influence on the water column microbiota, but a much weaker influence on the epibiota of neighbouring macroalgae. Overall, these results support the idea that macroalgae surfaces are highly selective and demonstrate that modulations of macroalgal microbiota operate within an overarching paradigm of host species specificity.

Alternate life history phases of a common seaweed have distinct microbial surface communities.

Macroalgal life histories are complex, often involving the alternation of distinct free-living life history phases that differ in morphology, longevity and ploidy. The surfaces of marine macroalgae support diverse microbial biofilms, yet the degree of microbial variation between alternate phases is unknown. We quantified bacterial (16S rRNA gene) and microeukaryote (18S rRNA gene) communities on the surface of the common intertidal seaweed, Mastocarpus spp., which alternates between gametophyte (foliose, haploid) and sporophyte (encrusting, diploid) life history phases. A large portion (97%) of bacterial taxa on the surface Mastocarpus was also present in samples from the environment, indicating that macroalgal surface communities are largely assembled from the surrounding seawater. Still, changes in the relative abundance of bacterial taxa result in significantly different communities on alternate Mastocarpus life history phases, rocky substrate and seawater at all intertidal elevations. For microeukaryote assemblages, only high intertidal samples had significant differences between life history phases although sporophytes were not different from the rocky substrate at this elevation; gametophytes and sporophytes did not differ in microeukaryote communities in the mid and low zones. By sequencing three host genes, we identified three cryptic species of Mastocarpus in our data set, which co-occur in the mid-to-low intertidal zone. In these samples, M. alaskensis sporophytes harboured distinct bacterial communities compared to M. agardhii and M. intermedius sporophytes, which were not distinguishable. Conversely, microeukaryote communities did not differ among species.

The benign helminth Hymenolepis diminuta ameliorates chemically induced colitis in a rat model system.

The tapeworm Hymenolepis diminuta is a model for the impact of helminth colonization on the mammalian immune system and a candidate therapeutic agent for immune mediated inflammatory diseases (IMIDs). In mice, H. diminuta protects against models of inflammatory colitis by inducing a strong type 2 immune response that is activated to expel the immature worm. Rats are the definitive host of H. diminuta, and are colonized stably and over long time periods without harming the host. Rats mount a mild type 2 immune response to H. diminuta colonization, but this response does not generally ameliorate colitis. Here we investigate the ability of different life cycle stages of H. diminuta to protect rats against a model of colitis induced through application of the haptenizing agent dinitrobenzene sulphonic acid (DNBS) directly to the colon, and monitor rat clinical health, systemic inflammation measured by TNFα and IL-1ß, and the gut microbiota. We show that immature H. diminuta induces a type 2 response as measured by increased IL-4, IL-13 and IL-10 expression, but does not protect against colitis. In contrast, rats colonized with mature H. diminuta and challenged with severe colitis (two applications of DNBS) have lower inflammation and less severe clinical symptoms. This effect is not related the initial type 2 immune response. The gut microbiota is disrupted during colitis and does not appear to play an overt role in H. diminuta-mediated protection.