Microbial Influence Research Articles

Soil microbes drive the effect of plant species and genotypic diversity interaction on productivity.

PurposeThe effect of plant species and genotypic diversity on productivity has been well documented but little is known about the contribution of the interaction between species and genotypic diversity. Since the influence of soil microorganisms on the plant diversity-productivity relationship is increasingly recognized, we investigated potential interactions between plant species diversity, plant genotypic diversity and soil microbes. We hypothesized that the non-additive effects of plant species and genotypic diversity on productivity could be microbe-driven.MethodsWe set up pea and wheat monocultures and mixtures in a growth chamber, varying for their levels of genotypic diversity under three different soil microbial contexts. We assessed plant shoot and root biomass production, soil mineral nitrogen content and described the soil bacterial communities.ResultsWe found that shoot biomass in mixtures involving both species and genotypic diversity was higher than expected considering the additive effects of plant species diversity and genotypic diversity. Rather than a synergy between two positive effects of species and genotypic diversity, we observed that species mixture compensated the negative effect of genotypic diversity. Regarding microbial influence, we found that the effect of plant species diversity, plant genotypic diversity and their interaction on productivity were all driven by the soil microbial community as no effect was observed in a pre-sterilised soil.ConclusionOur study suggests that the plant diversity-productivity relationship could be shaped by a three-way interaction between plant species diversity, plant genotypic diversity and soil microbes. Thus, plant-microbe and plant-plant interactions could be a determinant of the plant diversity-productivity relationship.

Land cover affects the breakdown of Pinus elliottii needles litter by microorganisms in soil and stream systems of subtropical riparian zones

Riparian zones are important interface areas between soil and stream systems. Few studies carried out in tropical and subtropical regions evaluate litter decomposition in both stream water and riparian soils. Herein, we assessed the effects of land cover on microbial activity on the decomposition of an exotic litter (Pinus elliottii pine needles only) in water and soils of a subtropical riparian zone. Leaf litter breakdown rates (k in d−1) were estimated for different land covers (Grassland without riparian vegetation, Grassland with riparian vegetation, Forest, and Silviculture). To assess the microbial influence on k, we used fine mesh litter bags with monospecific leaf litter of senescent pine needles. Streams in Silviculture land use showed high k values and orthophosphate, dissolved oxygen and water velocity accelerated the leaf litter breakdown in the stream system. The soil system of Silviculture, Forest, and Grassland with riparian vegetation land covers showed high k values due to the high moisture and litter stock on riparian soil. Only a minor difference between stream and soil systems highlights the significant changes and the negative effects of silviculture on subtropical riparian zones.

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression.

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA (trimethylamine), as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

Potential distributional shifts in North America of allelopathic invasive plant species under climate change models

Predictive studies play a crucial role in the study of biological invasions of terrestrial plants under possible climate change scenarios. Invasive species are recognized for their ability to modify soil microbial communities and influence ecosystem dynamics. Here, we focused on six species of allelopathic flowering plants—Ailanthus altissima, Casuarina equisetifolia, Centaurea stoebe ssp. micranthos, Dioscorea bulbifera, Lantana camara, and Schinus terebinthifolia—that are invasive in North America and examined their potential to spread further during projected climate change. We used Species Distribution Models (SDMs) to predict future suitable areas for these species in North America under several proposed future climate models. ENMEval and Maxent were used to develop SDMs, estimate current distributions, and predict future areas of suitable climate for each species. Areas with the greatest predicted suitable climate in the future include the northeastern and the coastal northwestern regions of North America. Range size estimations demonstrate the possibility of extreme range loss for these invasives in the southeastern United States, while new areas may become suitable in the northeastern United States and southeastern Canada. These findings show an overall northward shift of suitable climate during the next few decades, given projected changes in temperature and precipitation. Our results can be utilized to analyze potential shifts in the distribution of these invasive species and may aid in the development of conservation and management plans to target and control dissemination in areas at higher risk for potential future invasion by these allelopathic species.

Afforestation with Pinus sylvestris var. mongolica remodelled soil bacterial community and potential metabolic function in the Horqin Desert

Soil bacteria have been widely investigated and their roles in terrestrial ecosystems are relatively well understood. The soil bacterial community and potential function are controlled by vegetation and bacteria are factors indicating changes in soil microenvironment. However, there is a knowledge gap regarding microbial influence and their use to predict the change in metabolic function after afforestation in desert ecosystem. Pinus sylvestris var. mongolica is the most important evergreen species in desertified northern China. Therefore, we used the 16S rRNA high-throughput sequencing and PICRUSt platform to identify the soil bacterial community and potential metabolic function across stand ages (HQh: half-mature forest, HQn: nearly-mature forest, HQm: mature forest) and control (CK, natural grassland) in the Horqin Desert. Soil characteristics were determined to clarify edaphic driving factors and reveal the effect of afforestation on bacteria. The results indicated that (1) The dominant soil bacterial community category was stable but potential metabolic function changed across stand ages. The dominant phyla and genera were Proteobacteria and Acidobacteria and Sphingomonas, RB41, respectively; the metabolic functions changed from carbohydrate to amino acid metabolism. (2) P. sylvestris plantations significantly increased soil bacterial diversity (P < 0.05). Catalase was significantly correlated with soil bacterial diversity (P < 0.05). (3) The driving factor of the bacterial community was Urease in the CK plot. Afforestation changed the soil organic matter (SOM) in HQh and HQn, but urease was restored in HQm. The dominant soil characteristics that affected potential metabolic function were soil porosity (SP) and total nitrogen (TN) in the CK plot, total phosphorous (TP) and SOM in HQh, catalase activity in HQn, and urease in HQm. The changes in dominant soil characteristics forecasted that afforestation broke traditional desert grassland ecological balance, established a new forest ecological balance by changing soil environment, and indicated that the potential metabolic pattern changed from resource acquisition to resource utilization. This may herald the creation of new ecosystems in deserts. Our results provide strong microbial evidence that evaluated the significance of afforestation in arid regions.

Formation of Magnesium Carbonates on Earth and Implications for Mars.

Magnesium carbonates have been identified within the landing site of the Perseverance rover mission. This study reviews terrestrial analog environments and textural, mineral assemblage, isotopic, and elemental analyses that have been applied to establish formation conditions of magnesium carbonates. Magnesium carbonates form in five distinct settings: ultramafic rock-hosted veins, the matrix of carbonated peridotite, nodules in soil, alkaline lake, and playa deposits, and as diagenetic replacements within lime—and dolostones. Dominant textures include fine-grained or microcrystalline veins, nodules, and crusts. Microbial influences on formation are recorded in thrombolites, stromatolites, crinkly, and pustular laminites, spheroids, and filamentous microstructures. Mineral assemblages, fluid inclusions, and carbon, oxygen, magnesium, and clumped isotopes of carbon and oxygen have been used to determine the sources of carbon, magnesium, and fluid for magnesium carbonates as well as their temperatures of formation. Isotopic signatures in ultramafic rock-hosted magnesium carbonates reveal that they form by either low-temperature meteoric water infiltration and alteration, hydrothermal alteration, or metamorphic processes. Isotopic compositions of lacustrine magnesium carbonate record precipitation from lake water, evaporation processes, and ambient formation temperatures. Assessment of these features with similar analytical techniques applied to returned Martian samples can establish whether carbonates on ancient Mars were formed at high or low temperature conditions in the surface or subsurface through abiotic or biotic processes. The timing of carbonate formation processes could be constrained by 147Sm-143Nd isochron, U-Pb concordia, 207Pb-206Pb isochron radiometric dating as well as 3He, 21Ne, 22Ne, or 36Ar surface exposure dating of returned Martian magnesium carbonate samples.

Biogeographical Regionalization of Wine Yeast Communities in Greece and Environmental Drivers of Species Distribution at a Local Scale.

Recent research has expanded our understanding on vineyard-associated fungal community assembly, suggesting non-random distribution and implicating regional differences in the wine terroir effect. Here, we focused on the culturable fraction of the fungal community that resides on grapes and determine wine quality, the so-called wine yeast populations. We aimed to analyze local-scale yeast community assemblages and to test whether the hypothesis of biogeographical patterns also applies to wine yeasts in particular. Surveying 34 vineyards across four main viticultural zones in Greece showed significant trends in vineyard-specific patterns. At a local scale, viticultural regions were also linked to distinct yeast community compositions. Importantly, major yeast populations directly related to wine fermentation contributed significantly to the delimitation of regions, highlighting their potential influence on the regionality of wine characteristics. In terms of the microbial terroir influence, yeast communities within an area were temporarily stable, which is critical for the regional character of the wine. Community structure could be explained only partially by environmental features. Maximum temperature, elevation, and net precipitation were the highest correlated variables with the yeast community biogeographic patterns. Finally, we also showed that certain environmental factors may drive the population size of specific yeast populations. The present results indicate that the wine yeast community has a geographical character at local scale, which is an important feature of the microbial terroir concept and thus for the wine industry.

Teresa B. Fitzpatrick.

Teresa B. Fitzpatrick.

Onshore groundwater spring carbonate mounds to lacustrine microbialites, the perplexing record of a transitional Great Salt Lake carbonate shoreline at Lakeside, Utah

AbstractNon‐marine carbonates at Lakeside (Utah) are the depositional record of transitional shoreline palaeoenvironments around 1,285 m, as lake elevation fell from Lake Bonneville levels to low‐stand Great Salt Lake levels of 1,284–1,278 m. Lakeside carbonates provide a rare example of onshore groundwater spring deposits connected to lacustrine microbialite reefs. Clotted fabrics and mineralized bacteriomorphs suggest microbial influence both in groundwater spring and littoral carbonates. Thrombolitic clotted aragonite and dendritic clotted intermediate magnesium calcite may document two distinct microbial ecosystems each with a specific mineralogy. Radiocarbon dates from interior to outer layers of a 20 cm littoral microbialite suggest several thousand years of domal growth. Climate fluctuations may be recorded in littoral deposits by the alternation of ooids (increased salinity, arid conditions) with ostracods (fresher water, humid conditions). Successive higher frequency cycles of sedimentation, exposure, microkarst and early diagenesis were cemented by vadose and phreatic very high magnesium calcite and non‐stoichiometric dolomite. Several layers of littoral and beach deposits accumulated during longer lacustrine transgressive–regressive cycles. Clastic detritus and lack of known initial U and Th concentrations could explain the lack of correlation between widely scattered U‐Th ages and closely grouped 14C dates. Calibrated ages from radiocarbon dating may have been increased by long residence time of groundwater in bedrock, since 87Sr/86Sr signatures do indicate possible littoral‐zone mixing of lake water with groundwater from outcropping and subsurface Mississippian Great Blue Limestone. The perplexing Lakeside carbonate system is the result of interaction between microbial and chemical processes during sedimentation and early diagenesis.

Environmental and Microbial Influences on Corrosion of Selected Types of Petroleum Industry Steel

This study explored the influence of brackish water sediment, mangrove swamp sediment, clayey/lateritic soil, and river water (freshwater) sediment on the corrosion rates of carbon, mild, and stainless steels and the species of sulphate reducing bacteria (SRB) and iron bacteria associated with the process. The material loss following burial of the steel samples for a 9-month period was assessed. Standard and specialised microbiological techniques were employed in the characterisation of the bacterial species. Qualitative assessment for corrosion was done via optical microscopy and macroscopy. Corrosion was highest on steel buried in brackish water sediment and lowest in that from river water sediment. Carbon steel was the most susceptible to corrosion while stainless steel was the most resistant. Sulphite, sulphide, nitrate and phosphate concentrations had a strong impact on corrosion rates. Thiobacillus, Leptothrix and Gallionella dominated amongst the iron bacteria while Desulfobacter and Desulfovibrio dominated amongst the SRB. There were significant differences in corrosion rates and bacterial abundance from one environment to the other. Iron bacteria showed greater abundance than SRB across the different environments and steel types. Iron bacteria counts, however, did not correlate positively with corrosion rates. The findings suggest that oil industry facilities in brackish water environments are more liable to corrosion than those located in fresh water ecosystems.

How do soil microbes exert impact on soil respiration and its temperature sensitivity?

Understanding how soil microorganisms influence the direction and magnitude of soil carbon feedback to global warming is vital to predict future climate change. Although microbial activities are major contributors to soil respiration (RS ) and its temperature sensitivity (Q10 ), the mechanisms underpinning microbial influence on RS and Q10 remain unclear. Coupling variation partitioning analysis (VPA), correlation analysis and multiple stepwise linear regression analysis, we illustrate that bacteria mainly affect RS and its temperature sensitivity (Q10 ) by shifting bacterial community composition (denoted by principal coordinates analysis). We also found that soil water content (SWC) and available nutrient (AN) were the factor key to changing bacterial community composition (P<0.05). Co-occurrence network demonstrated that Mod 0 ecological cluster composed of copiotrophic taxa groups was significantly associated with RS and Q10 (P< 0.01, R> 0.5), including Proteobacteria, Actinobacteria, and Bacteroidetes. Illuminating the mechanisms underpinning the influence of soil microbes on RS and Q10 values is fundamental to understanding mechanistic soil-climate carbon cycles.

Difference and interplay of microbial communities, metabolic functions, trophic modes and influence factors between sludge and bulking agent in a composting matrix

The difference and interplay of microbial communities, metabolic functions and influence factors between sewage sludge and bulking agent were evaluated in 60 days composting. Results showed that fungal communities were mainly affected by pH (42.4%) and ORP (35.9%) of sludge but by VS (41.1%) and temperature (34.7%) of sawdust in a composting system. Bacterial communities were primarily affected by VS (43.5%) and C/N (34.8%) of sludge but by ORP (44.5%) and temperature (31.0%) of sawdust. Tepidimicrobium dominated in the sludge at thermophilic period, while Alcaligenes prevailed in the sawdust. Bacterial carbon metabolism was significantly higher in the sludge than that in the sawdust except carbohydrate metabolism. Saprophytic fungi were the main trophic mode both in the sludge and sawdust. Water transfer facilitated Aspergillus and Trichosporon moving from sludge to sawdust to decompose lignocellulose. Ammonia transfer promoted the migration of Alcaligenes and Pseudomonas from sludge to sawdust and facilitated ammonia assimilating.

Effect of Multispecies Microbial Consortia on Microbially Influenced Corrosion of Carbon Steel

Microbially influenced corrosion (MIC) is responsible for significant damage to major marine infrastructure worldwide. While the microbes responsible for MIC typically exist in the environment in a synergistic combination of different species, the vast majority of laboratory-based MIC experiments are performed with single microbial pure cultures. In this work, marine grade steel was exposed to a single sulfate reducing bacterium (SRB, Desulfovibrio desulfuricans) and various combinations of bacteria (both pure cultures and mixed communities), and the steel corrosion studied. Differences in the microbial biofilm composition and succession, steel weight loss and pitting attack were observed for the various test configurations studied. The sulfate reduction phenotype was successfully shown in half-strength marine broth for both single and mixed communities. The highest corrosion according to steel weight loss and pitting, was recorded in the tests with D. desulfuricans alone when incubated in a nominally aerobic environment. The multispecies microbial consortia yielded lower general corrosion rates compared to D. desulfuricans or for the uninoculated control.

Plant Holobiont Theory: The Phytomicrobiome Plays a Central Role in Evolution and Success.

Under natural conditions, plants are always associated with a well-orchestrated community of microbes—the phytomicrobiome. The nature and degree of microbial effect on the plant host can be positive, neutral, or negative, and depends largely on the environment. The phytomicrobiome is integral for plant growth and function; microbes play a key role in plant nutrient acquisition, biotic and abiotic stress management, physiology regulation through microbe-to-plant signals, and growth regulation via the production of phytohormones. Relationships between the plant and phytomicrobiome members vary in intimacy, ranging from casual associations between roots and the rhizosphere microbial community, to endophytes that live between plant cells, to the endosymbiosis of microbes by the plant cell resulting in mitochondria and chloroplasts. If we consider these key organelles to also be members of the phytomicrobiome, how do we distinguish between the two? If we accept the mitochondria and chloroplasts as both members of the phytomicrobiome and the plant (entrained microbes), the influence of microbes on the evolution of plants becomes so profound that without microbes, the concept of the “plant” is not viable. This paper argues that the holobiont concept should take greater precedence in the plant sciences when referring to a host and its associated microbial community. The inclusivity of this concept accounts for the ambiguous nature of the entrained microbes and the wide range of functions played by the phytomicrobiome in plant holobiont homeostasis.

Extracellular vesicle-derived microbiome obtained from exhaled breath condensate in patients with asthma

Extracellular vesicle-derived microbiome obtained from exhaled breath condensate in patients with asthma

Preparation, Properties, and Microbial Impact of Tungsten (VI) Oxide and Zinc (II) Oxide Nanoparticles Enriched Polyethylene Sebacate Nanocomposites

Nanoparticles of tungsten oxide (WO3) and zinc oxide (ZnO) enriched polyethylene sebacate (PES) nanocomposites were prepared through the coprecipitation process and condensation polymerization reaction. The obtained nano-sized particles of WO3 and ZnO, PES, and nanocomposites (WO3-PES NC and ZnO-PES NC) were investigated. The average molecular weight of the cured PES was measured by employing the gel permeation chromatography (GPC) technique. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) spectra assured the formation of the polymeric nanocomposites.WO3 and ZnO nanoparticles supposed a condensed porous spherical phase found implanted in the polymer structure, as detected by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. These nano-scale systems achieved an electrical activity based on the conductive nanoparticles embedded matrix as a result of the ion–ion interactions. The microbial influence of the nanocomposites was examined against pathogenic bacteria; Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, and Fungi; Aspergillus niger, and Candida albicans. Results exhibited that these nanocomposites have antimicrobial effects from moderate to slightly high on bacteria and high on fungi which was confirmed by a clear zone of inhibition. This study contributes to the design of reasonable composites to be under evaluation for their catalytic effect.

Model for calcite spherulite formation in organic, clay-rich, lacustrine carbonate shales (Barbalha Formation, Aptian, Araripe Basin, NE Brazil)

The formation of carbonate spherulites, recognized as part of the South-Atlantic Pre-Salt reservoir rocks, remains enigmatic. Well-chosen analogues provide insights into depositional and diagenetic conditions and the biotic versus abiotic processes that might influence or even control spherulite growth. Radial fibrous calcite spherulites of the Batateira beds in the Barbalha Formation (Aptian, Araripe, NE Brazil) formed mainly in organic and clay-rich laminite layers as nodules that grew around different nuclei, now represented by, amongst others, micrite and apatite ostracods. They vertically alternate with clays, but also carbonate laminites, which locally also contain spherulites. Characterization of the organic matter content of spherulitites (petrography, total organic carbon, vitrinite reflectance, stable isotopes) reveals TOC's of up to 30% related to the presence of mainly oil-prone alginite next to huminite, inertinite, sporinites and zooclasts. The complex mixture of clays, dominantly autogenic mixed layered illite-montmorrilonite, which alternate with lacustrine carbonates and evaporites, is diagnostic for lakes in a semi-arid environment. The occurrence of gypsum, calcitic alveolar honeycomb spherulite textures, preferential concentration of pyrite at the spherulite-matrix contact and inward spherulite perforations suggest bacterial activity under shallow and evaporitic syn-depositional conditions. Although the Barbalha spherulites formed chemically-driven in a viscous matrix, the microbial influence, mainly as lamalginite in the clayey matrix, is undeniable. The mixed organic-silicate gel catalyzed calcite spherulite formation. The Barbalha spherulites consequently illustrate the complementary influence of clays, organic matter and evaporitic syn-sedimentary conditions.

Abstract PO034: Mechanisms and microbial Influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: A narrative review

Abstract Background: The relationship between gastrointestinal (GI) bacteria and the response to anti-CTLA-4 and anti-PD-1 immunotherapy in the treatment of cancer can potentially be enhanced to allow patients to maximally respond to these treatments. Insight into the complex interaction between gut microbiota and the human adaptive immune system will help guide future immunotherapeutic cancer treatments to allow a more robust clinical response and fewer adverse effects in patients requiring these drugs. This review highlights these interactions as well as the potential for the creation of “oncomicrobiotics” that would selectively tailor one’s GI bacteria to maximally respond to anti-CTLA-4 and anti-PD-1 treatments. Main Body: CTLA-4 is an antigen on the surface of T cells which, upon stimulation, leads to inhibition of activated T cells to terminate the immune response. However, many types of tumor cells can upregulate CTLA-4 in the tumor microenvironment, allowing these cells to evade targeting and destruction by the body’s immune system by prematurely inhibiting T cells. Increased representation of Bacteriodes fragilis and Burkholderia cepacia in the GI tract of patients receiving CTLA-4-based immunotherapy led to a stronger therapeutic effect while minimizing adverse side effects such as colitis. In addition, introducing bacteria involved in vitamin B and polyamine transport to the GI tracts of patients treated with anti-CTLA-4 drugs led to increased resistance to colitis while maintaining therapeutic efficacy. PD-1 is another molecule upregulated in many tumor microenvironments which acts in a similar manner to CTLA-4 to tone down the anti-neoplastic actions of T cells. Antibodies to PD-1 have shown promise to help allow the body’s natural immune response to appropriately target and destroy tumor cells. The presence of Bifidobacterium, namely Bifidobacterium breve and longum, in the GI tracts of cancer patients has the potential to create a more robust immune response to anti-PD-1 drugs while limiting medication-induced adverse effects. The development of “oncomicrobiotics” has the potential to help tailor one’s gut microbiota to allow patients to maximally respond to immunotherapy without sacrificing increases in toxicity. These oncomicrobiotics may possibly include antibiotics, probiotics, postbiotics and/or prebiotics. However, many challenges lie ahead in the creation of oncomicrobiotics. Conclusion: The creation of oncomicrobiotics may allow many patients receiving anti-CTLA-4 and PD-1 immunotherapy to experience prolonged survival and a better quality of life. Citation Format: Peter L. Miller, Tiffany L. Carson. Mechanisms and microbial Influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: A narrative review [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO034.

Study on the preparation conditions and degradation performance of an efficient immobilized microbial agent for marine oil pollution

ABSTRACT In the process of handling marine oil spills accidents, the biological method has attracted wide attention due to its low cost and no secondary pollution. However, in the process of practical application, there are problems such as low microbial density and great influence of environmental factors when the oil is treated by spraying microorganisms on the sea surface. This study used immobilized microorganism technology to solve the above-mentioned problems. In this study, the bacteria immobilized on cinnamon shell (CS) with good degradation performance were obtained by optimizing preparation conditions. Under the optimal conditions of sodium alginate (SA) concentration of 4.57%, CS concentration of 1.28%, and the CaCl2 concentration of 2.45%, the degradation rate of diesel in 5 days reached 74.04%. The reusability of immobilized microbial agents was further studied. The study designed three cycles of repeated degradation experiments. The results showed that the degradation rate of diesel can still reach 60.12% after three times of reuse, which indicated the reusability of the immobilized microbial agents was excellent. The decrease in degradation rate of diesel was mainly related to the fragmentation of immobilized microbial agents and the decrease in microbial biomass.

Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy.

Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.