Gut Mucus Research Articles

Insights into the gut microbiome of vitiligo patients from India

BackgroundVitiligo is an autoimmune disease characterized by loss of pigmentation in the skin. It affects 0.4 to 2% of the global population, but the factors that trigger autoimmunity remain elusive. Previous work on several immune-mediated dermatological disorders has illuminated the substantial roles of the gut microbiome in disease pathogenesis. Here, we examined the gut microbiome composition in a cohort of vitiligo patients and healthy controls from India, including patients with a family history of the disease.ResultsOur results show significant alterations in the gut microbiome of vitiligo patients compared to healthy controls, affecting taxonomic and functional profiles as well as community structure. We observed a reduction in the abundance of several bacterial taxa commonly associated with a healthy gut microbiome and noted a decrease in the abundance of SCFA (Short Chain Fatty Acids) producing taxa in the vitiligo group. Observation of a higher abundance of genes linked to bacteria-mediated degradation of intestinal mucus suggested a potential compromise of the gut mucus barrier in vitiligo. Functional analysis also revealed a higher abundance of fatty acid and lipid metabolism-related genes in the vitiligo group. Combined analysis with data from a French cohort of vitiligo also led to the identification of common genera differentiating healthy and gut microbiome across populations.ConclusionOur observations, together with available data, strengthen the role of gut microbiome dysbiosis in symptom exacerbation and possibly pathogenesis in vitiligo. The reported microbiome changes also showed similarities with other autoimmune disorders, suggesting common gut microbiome-mediated mechanisms in autoimmune diseases. Further investigation can lead to the exploration of dietary interventions and probiotics for the management of these conditions.

Mucin-driven ecological interactions in an in vitro synthetic community of human gut microbes.

Specific human gut microbes inhabit the outer mucus layer of the gastrointestinal tract. Certain residents of this niche can degrade the large and complex mucin glycoproteins that constitute this layer and utilise the degradation products for their metabolism. In turn, this microbial mucin degradation drives specific microbiological ecological interactions in the human gut mucus layer. However, the exact nature of these interactions remains unknown. In this study, we designed and studied an in vitro mucin-degrading synthetic community that included mucin O-glycan degraders and cross-feeding microorganisms by monitoring community composition and dynamics through a combination of 16S rRNA gene amplicon sequencing and qPCR, mucin glycan degradation with PGC-LC-MS/MS, production of mucin-degrading enzymes and other proteins through metaproteomics, and metabolite production with HPLC. We demonstrated that specialist and generalist mucin O-glycan degraders stably co-exist and found evidence for cross-feeding relationships. Cross-feeding on the products of mucin degradation by other gut microbes resulted in butyrate production, hydrogenotrophic acetogenesis, sulfate reduction and methanogenesis. Metaproteomics analysis revealed that mucin glycan degraders Akkermansia muciniphila, Bacteroides spp. and Ruminococcus torques together contributed 92% of the total mucin O-glycan degrading enzyme pool of this community. Furthermore, comparative proteomics showed that in response to cultivation in a community compared to monoculture, mucin glycan degraders increased carbohydrate-active enzymes whereas we also found indications for niche differentiation. These results confirm the complexity of mucin-driven microbiological ecological interactions and the intricate role of carbohydrate-active enzymes in the human gut mucus layer.

Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer

The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC∆Chil1 mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a ‘scaffold model’ for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.

Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer.

The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC∆Chil1 mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a 'scaffold model' for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.

Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis

BackgroundEnterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke (AIS). Accumulative evidence suggests that mesenchymal stem cell (MSC) effectively ameliorates stroke outcomes. Whether MSC...

Feedback delivery of BMP 7 on the pathological oxidative stress via smart hyaluronic acid hydrogel potentiated the repairing of the gut epithelial integrity

The intestinal barrier integrity was substantially collapsed when colitis flaring up, accompanying by the hallmark of pathological oxidative stress. Bone morphogenetic protein 7 (BMP 7), an endogenous growth factor in gut had the potential to repair the damaged mucosa. Herein, a smart hydrogel (HDP) had been developed by the boronate-ester crosslinked hyaluronic acid to deliver BMP 7. Hydrogel loading BMP 7 (HDP-BMP 7) presented the comparable mechanical strength with that of the naïve gut mucus. HDP-BMP 7 as artificial mucus could specifically adhere to the inflamed colonic mucosa of colitis mice. Importantly, it could apperceive reactive oxygen species at diseased colon to adapt its intrinsic network, enabling the feedback release of BMP 7 on the pathological oxidative stress. Moreover, in vivo animal experiments showed that the disease symptoms of colitis mice were alleviated by HDP-BMP 7. Importantly, both the mucus barrier and the epithelial barriers were obviously recovered by HDP-BMP 7 treatment, which substantially attenuated the immune-inflammation response of colitis mice. Besides, HDP-BMP 7 enriched the diversity of gut flora, increasing the relative abundance of Lactobacillus and decreasing the ratio of Firmicutes/Bacteroidetes. Its therapeutic mechanism was associated with activating TGF-β/Smad signals. Conclusively, this smart hydrogel might potentiate the repairing effect of growth factors on the gut epithelial integrity.

Intratumoral microbiome of adenoid cystic carcinomas and comparison with other head and neck cancers

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.

Hydrogel Derived from Decellularized Porcine Small Intestinal Submucosa as a Physical Shielding Repaired the Gut Epithelial Barrier of Murine Ulcerative Colitis

AbstractUlcerative colitis (UC) is associated with the shedding of the gut mucus. Decellularized porcine small intestinal submucosa (SIS‐ECM) contains numerous active forms of extracellular matrix as well as growth factors. Herein, a mucus‐mimetic hydrogel (MAG) is designed as a barrier therapy by integrating SIS‐ECM with hyaluronic acid and epigallocatechin‐3‐gallate. MAG not only presented the viscoelastic behaviors with G' of 4000 Pa but also good thixotropy. Moreover, MAG as a physical shielding is effective to hinder E. coli invasion. Besides, the good repairing effect on the injured Caco‐2 cells is presented by MAG. When MAG as a biomimetic mucus is rectally administrated to colitis mouse, it alleviated effectively the colitis symptoms and improved the colonic shorting. Moreover, expression of IL‐1β, IL‐6, and TNF‐α at the laminae propria is substantially inhibited by MAG. Besides, the colonic epitheliums are well rearranged, and the tight junction proteins (ZO‐1, Occludin‐1, Claudin‐5) between them are greatly upregulated after MAG treatment. Meanwhile, the mucus secretion of goblets cells is effectively repaired by MAG treatment. The repairing mechanism of intestinal mucosa barriers is associated with promoting the proliferation and differentiation of intestinal stem cells. Collectively, MAG might be a promising strategy of barrier therapy for UC.

Competing mechanisms in bacterial invasion of human colon mucus probed with agent-based modeling

The gastrointestinal tract is inhabited by a vast community of microorganisms, termed the gut microbiota. Large colonies can pose a health threat, but the gastrointestinal mucus system protects epithelial cells from microbiota invasion. The human colon features a bilayer of mucus lining. Due to imbalances in intestinal homeostasis, bacteria may successfully penetrate the inner mucus layer, which can lead to severe gut diseases. However, it is hard to tease apart the competing mechanisms that lead to this penetration. To probe the conditions that permit bacteria penetration into the inner mucus layer, we develop an agent-based model consisting of bacteria and an inner mucus layer subject to a constant flux of nutrient fields feeding the bacteria. We find that there are three important variables that determine bacterial invasion: the bacterial reproduction rate, the contact energy between bacteria and mucus, and the rate of bacteria degrading the mucus. Under healthy conditions, all bacteria are naturally eliminated by the constant removal of mucus. In diseased states, imbalances between the rates of bacterial degradation and mucus secretion lead to bacterial invasion at certain junctures. We conduct uncertainty quantification and sensitivity analysis to compare the relative impact between these parameters. The contact energy has the strongest influence on bacterial penetration, which, in combination with bacterial degradation rate and growth rate, greatly accelerates bacterial invasion of the human gut mucus lining. Our findings will serve as predictive indicators for the etiology of intestinal diseases and highlight important considerations when developing gut therapeutics.

Insect live larvae as a new nutritional model in duck: effects on gut health

BackgroundThis study aimed to evaluate the effects of Hermetia illucens (Black soldier fly-BSF) and Tenebrio molitor (Yellow mealworm-YMW) live larvae as a new nutritional model on duck’s gut health, considering gut histomorphometry, mucin composition, cytokines transcription levels, and microbiota. A total of 126, 3-days-old, females Muscovy ducks were randomly allotted to three dietary treatments (6 replicates/treatment, 7 birds/pen): (i) C: basal diet; (ii) BSF: C + BSF live larvae; (iii) YMW: C + YMW live larvae. BSF and YMW live larvae were administered on top of the basal diet, based on the 5% of the expected daily feed intake. The live weight, average daily gain, average daily feed intake and feed conversion ratio were evaluated for the whole experimental period. On day 52, 12 ducks/treatment (2 birds/replicate) were slaughtered and samples of duodenum, jejunum, ileum, spleen, liver, thymus and bursa of Fabricius were collected for histomorphometry. Mucin composition was evaluated in the small intestine through histochemical staining while jejunal MUC-2 and cytokines transcription levels were evaluated by rt-qPCR. Cecal microbiota was also analyzed by means of 16 S rRNA gene sequencing.ResultsBirds’ growth performance and histomorphometry were not influenced by diet, with a proximo-distal decreasing gradient from duodenum to ileum (p < 0.001), respecting the physiological gut development. Mucin staining intensity and MUC-2 gene expression did not vary among dietary treatments, even though mucin intensity increased from duodenum to ileum, according to normal gut mucus physiology (p < 0.001). Regarding local immune response, IL-6 was higher in YMW group when compared to the other groups (p = 0.009). Insect live larvae did not affect cecal microbiota diversity, but BSF and YMW groups showed a higher presence of Helicobacter, Elusimicrobium, and Succinatimonas and a lower abundance of Coriobacteriaceae and Phascolarctobacterium compared to C birds (p < 0.05).ConclusionsThe use of BSF and YMW live larvae as new nutritional model did not impair gut development and mucin composition of Muscovy ducks, but slightly improved the intestinal immune status and the microbiota composition by enhancing regulatory cytokine IL-6 and by increasing minor Operational Taxonomic Units (OTUs) involved in short-chain fatty acids production.

The immune interactions of gut glycans and microbiota in health and disease.

The human digestive system harbors a vast diversity of commensal bacteria and maintains a symbiotic relationship with them. However, imbalances in the gut microbiota accompany various diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancers (CRCs), which significantly impact the well-being of populations globally. Glycosylation of the mucus layer is a crucial factor that plays a critical role in maintaining the homeostatic environment in the gut. This review delves into how the gut microbiota, immune cells, and gut mucus layer work together to establish a balanced gut environment. Specifically, the role of glycosylation in regulating immune cell responses and mucus metabolism in this process is examined.

Lacticaseibacillusparacasei BNCC345679 revolutionizes DSS-induced colitis and modulates gut microbiota.

The gut microbiota plays an important role in the disease progression of inflammatory bowel disease. Although probiotics are effective against IBD, not many studies have investigated their effects on gut microbiota composition and immunomodulation in mouse colitis models. Our study aimed at the therapeutic effects of Lacticaseibacillus paracasei BNCC345679 for the first time and explored its impact on gut microbiome dysbiosis, inflammatory cytokines, related miRNAs, VCAM-1, oxidative stress, intestinal integrity, and mucus barrier. We found that oral intervention of L. paracasei BNCC345679 affects recovering beneficial microbial taxa, including lactobacillus spp. and akkermansia spp., followed by improved body weight, DAI score, and inflammatory cytokines. L. paracasei BNCC345679 mitigated oxidative stress and increased the expression of intestinal integrity proteins MUC2 and ZO-1. These results suggested that L. paracasei BNCC345679 has the capacity to reduce DSS-induced colitis and has the potential as a supplement for the mitigation of IBD.

Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice

Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.

Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers.

The pathogenesis of ulcerative colitis (UC) is associated with the shedding of the gut mucus. Herein, inspired by the biological functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK) was designed for UC treatment by integrating dihydrocaffeic acid-modified poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive factors (KPV tripeptide and epidermal growth factor). PHE-EK presented good thermosensitive properties, as a flowable liquid at room temperature and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel presented good mechanical strength with a strain of 77.8%. Moreover, PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo adhesive tests showed that the PHE-EK hydrogel could specifically adhere to the inflamed colon via electrostatic interaction. When PHE-EK as a biomimetic mucus was rectally administrated to colitis rats, it effectively hindered the body weight loss, reduced the disease activity index and improved the colonic shorting. Moreover, the expression of pro-inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) at the laminae propria or epitheliums of the colon for colitis rats was substantially inhibited by PHE-EK. Besides, the colonic epitheliums were well rearranged, and the tight junction proteins (Zonula-1 and Claudin-5) between them were greatly upregulated after PHE-EK treatment. Collectively, PHE-EK might be a promising therapy for UC.

Interactions between intestinal microbial fermentation products of Pleurotus eryngii polysaccharide with gut mucus.

Recently, Pleurotus eryngii (P. eryngii) polysaccharide (PEP) has received a lot of attention from many researchers as the primary active substance. The PEP influences the gut microbiota in several ways, including the interaction of fermentation products with the intestinal mucus layer (IML) and intestinal epithelial cells. Herein, we characterized interactions between the IML and PEP after degradation by the gut microbes. Our results showed that fermented P. eryngii polysaccharide (FPEP) can interact with intestinal mucus (IM), and this interaction can reduce the degree of molecular aggregation of polysaccharides. At the same time, the fermentation time of FPEP also affects the interaction between the two. SEM showed that the FPEP solution tended to aggregate into larger particles, while with the addition of IM, the FPEP molecules were dispersed. Particle size measurements unveil substantial differences in the fermented polysaccharides' particle size between the group with supplementary IM (0 hours of fermentation: 485.1 ± 11.3 nm) and the group without IM (0 hours of fermentation: 989.33 ± 21.3 nm). Remarkably, within the group with added IM, the particle size reached its maximum at 24 hours of fermentation (585.87 ± 42.83 nm). Additionally, turbidity assessments demonstrate that, during the 12-hour interaction period, the 24-hour fermented polysaccharides consistently exhibit the highest OD values, ranging between 0.57 and 0.61. This work investigates the interaction between FPEP and IM, predicting the adhesion of polysaccharides to IM. Meanwhile, this provides a theoretical basis for further studies on the absorption and transport pathways of PEP and provides a novel research viewpoint on intestinal digestion and absorption.

Extraction of Mucins from the Mammalian Intestinal Tract.

In the intestine, mucus covering the mucosa plays a critical role in maintaining gut homeostasis by protecting the mucosa from invasion by commensal bacteria. The gut mucus is composed primarily of MUC2 mucin secreted by goblet cells. MUC2 is highly O-glycosylated, and O-glycans are necessary for the function and polymer structure of MUC2. In addition, recent evidence revealed that several glycan modifications, such as sialylation and sulfation, confer resistance of mucins to proteolysis and affect the viscosity and lubricity of mucus. Therefore, characterizing glycan structures of mucins is required to understand their functions fully. In this chapter, we describe how to purify secreted mucins from the mammalian intestine for analysis of their glycan structures. This description includes the extraction of MUC2 mucin from the mucosal surface of the mouse colon and colon explants.

Microbiome pattern and diversity of an anadromous fish, hilsa shad (Tenualosa ilisha).

The host-microbe interactions are complex, dynamic and context-dependent. In this regard, migratory fish species like hilsa shad (Tenualosa ilisha), which migrates from seawater to freshwater for spawning, provides a unique system for investigating the microbiome under an additional change in fish's habitat. This work was undertaken to detect taxonomic variation of microbiome and their function in the migration of hilsa. The study employed 16S rRNA amplicon-based metagenomic analysis to scrutinize bacterial diversity in hilsa gut, skin mucus and water. Thus, a total of 284 operational taxonomic units (OTUs), 9 phyla, 35 orders and 121 genera were identified in all samples. More than 60% of the identified bacteria were Proteobacteria with modest abundance (> 5%) of Firmicutes, Bacteroidetes and Actinobacteria. Leucobacter in gut and Serratia in skin mucus were the core bacterial genera, while Acinetobacter, Pseudomonas and Psychrobacter exhibited differential compositions in gut, skin mucus and water. Representative fresh-, brackish- and seawater samples of hilsa habitats were primarily composed of Vibrio, Serratia and Psychrobacter, and their diversity in seawater was significantly higher (P < 0.05) than freshwater. Overall, salinity and water microbiota had an influence on the microbial composition of hilsa shad, contributing to host metabolism and adaptation processes. This pioneer exploration of hilsa gut and skin mucus bacteria across habitats will advance our insights into microbiome assembly in migratory fish populations.

Effects of plant-based proteins and handling stress on intestinal mucus microbiota in rainbow trout

Via 16S rRNA gene amplicon sequencing, this study explores whether the gut mucus microbiota of rainbow trout is affected by the interaction of a plant-protein-based diet and a daily handling stressor (chasing with a fishing net) across two genetic lines (A, B). Initial body weights of fish from lines A and B were 124.7 g and 147.2 g, respectively. Fish were fed 1.5% of body weight per day for 59 days either of two experimental diets, differing in their fish meal [fishmeal-based diet (F): 35%, plant-based diet (V): 7%] and plant-based protein content (diet F: 47%, diet V: 73%). No diet- or stress-related effect on fish performance was observed at the end of the trial. However, we found significantly increased observed ASVs in the intestinal mucus of fish fed diet F compared to diet V. No significant differences in Shannon diversity could be observed between treatments. The autochthonous microbiota in fish fed with diet V was dominated by representatives of the genera Mycoplasma, Cetobacterium, and Ruminococcaceae, whereas Enterobacteriaceae and Photobacterium were significantly associated with diet F. The mucus bacteria in both genetic lines were significantly separated by diet, but neither by stress nor an interaction, as obtained via PERMANOVA. However, pairwise comparisons revealed that the diet effect was only significant in stressed fish. Therefore, our findings indicate that the mucus-associated microbiota is primarily modulated by the protein source, but this modulation is mediated by the stress status of the fish.

Fish gut and skin microbiota dysbiosis induced by exposure to commercial sunscreen formulations

UV filters (organic or mineral) present in sunscreen products are emerging contaminants of coastal aquatic environments. There is an urgent need to understand marine organisms responses to these compounds. In this study, we investigated the effect of exposure to dilutions of commercial sunscreen formulations on bacterial communities of mullet (Chelon sp.). The gut and skin mucus microbial communities were characterized using a metabarcoding approach targeting the 16S rRNA gene. Our results revealed that mullets had its own bacterial communities that differ from their surrounding habitats and specific to tissue. The dilutions of commercial sunscreens modified the relative abundance of Actinobacteroita, Bacteriodota and Proteobacteria for both gut and skin microbiota. They also allowed to bacteria affiliated to Mycobacterium, Nocardia and Tenacibaculum genera, known to house pathogenic species, to colonize the epithelium which may have implications for fish host health.

A novel on-a-chip system with a 3D-bioinspired gut mucus suitable to investigate bacterial endotoxins dynamics

The possible pathogenic impact of pro-inflammatory molecules produced by the gut microbiota is one of the hypotheses considered at the basis of the biomolecular dialogue governing the microbiota-gut-brain axis. Among these molecules, lipopolysaccharides (LPS) produced by Gram-negative gut microbiota strains may have a potential key role due to their toxic effects in both the gut and the brain.In this work, we engineered a new dynamic fluidic system, the MINERVA device (MI-device), with the potential to advance the current knowledge of the biological mechanisms regulating the microbiota-gut molecular crosstalk. The MI-device supported the growth of bacteria that are part of the intestinal microbiota under dynamic conditions within a 3D moving mucus model, with features comparable to the physiological conditions (storage modulus of 80 ± 19 Pa, network mesh size of 41 ± 3 nm), without affecting their viability (∼ 109 bacteria/mL). The integration of a fluidically optimized and user-friendly design with a bioinspired microenvironment enabled the sterile extraction and quantification of the LPS produced within the mucus by bacteria (from 423 ± 34 ng/mL to 1785 ± 91 ng/mL). Compatibility with commercially available Transwell-like inserts allows the user to precisely control the transport phenomena that occur between the two chambers by selecting the pore density of the insert membrane without changing the design of the system. The MI-device is able to provide the flow of sterile medium enriched with LPS directly produced by bacteria, opening up the possibility of studying the effects of bacteria-derived molecules on cells in depth, as well as the assessment and characterization of their effects in a physiological or pathological scenario.