Relationship between deltamethrin resistance and gut symbiotic bacteria of Aedes albopictus by 16S rDNA sequencing.

BACKGROUND: Aedes albopictus is an important vector for pathogens such as dengue, Zika, and chikungunya viruses. While insecticides is the mainstay for mosquito control, their widespread and excessive use has led to the increased resistance in Ae. albopictus globally. Gut symbiotic bacteria are believed to play a potential role in insect physiology, potentially linking to mosquitoes' metabolic resistance against insecticides. METHODS: We investigated the role of symbiotic bacteria in the development of resistance in Ae. albopictus by comparing gut symbiotic bacteria between deltamethrin-sensitive and deltamethrin-resistant populations. Adults were reared from field-collected larvae. Sensitive and resistant mosquitoes were screened using 0.03% and 0.09% deltamethrin, respectively, on the basis of the World Health Organization (WHO) tube bioassay. Sensitive and resistant field-collected larvae were screened using 5 × LC50 (lethal concentration at 50% mortality) and 20 × LC50 concentration of deltamethrin, respectively. Laboratory strain deltamethrin-sensitive adults and larvae were used as controls. The DNA of gut samples from these mosquitoes were extracted using the magnetic bead method. Bacterial 16S rDNA was sequenced using BGISEQ method. We isolated and cultured gut microorganisms from adult and larvae mosquitoes using four different media: Luria Bertani (LB), brain heart infusion (BHI), nutrient agar (NA), and salmonella shigella (SS). RESULTS: Sequencing revealed significantly higher gut microbial diversity in field-resistant larvae compared with field-sensitive and laboratory-sensitive larvae (P < 0.01). Conversely, gut microorganism diversity in field-resistant and field-sensitive adults was significantly lower compared with laboratory-sensitive adults (P < 0.01). At the species level, 25 and 12 bacterial species were isolated from the gut of field resistant larvae and adults, respectively. The abundance of Flavobacterium spp., Gemmobacter spp., and Dysgonomonas spp. was significantly higher in the gut of field-resistant larvae compared with sensitive larvae (all P < 0.05). Furthermore, the abundance of Flavobacterium spp., Pantoea spp., and Aeromonas spp. was significantly higher in the gut of field-resistant adults compared with sensitive adults (all P < 0.05). The dominant and differentially occurring microorganisms were also different between resistant larval and adult mosquitoes. These findings suggest that the gut commensal bacteria of Ae. albopictus adults and larvae may play distinct roles in their deltamethrin resistance. CONCLUSIONS: This study provides an empirical basis for further exploration of the mechanisms underlying the role of gut microbial in insecticide resistance, potentially opening a new prospect for mosquito control strategies.

Three-domain microbial communities in the gut of Pachnoda marginata larvae: A comparative study revealing opposing trends in gut compartments.

This study aimed to examine the bacterial, methanogenic archaeal, and eukaryotic community structure in both the midgut and hindgut of Pachnoda marginata larvae using an amplicon sequencing approach. The goal was to investigate how various diets and the soil affect the composition of these three-domain microbial communities within the gut of insect larvae. The results indicated a notable variation in the microbial community composition among the gut compartments. The majority of the bacterial community in the hindgut was composed of Ruminococcaceae and Christensenellaceae. Nocardiaceae, Microbacteriaceae, and Lachnospiraceae were detected in midgut samples from larvae feeding on the leaf diet, whereas Sphingomonadaceae, Rhodobacteraceae, and Promicromonasporaceae dominated the bacterial community of midgut of larvae feeding on the straw diet. The diet was a significant factor that influenced the methanogenic archaeal and eukaryotic community patterns. The methanogenic communities in the two gut compartments significantly differed from each other, with the midgut communities being more similar to those in the soil. A higher diversity of methanogens was observed in the midgut samples of both diets compared to the hindgut. Overall, the microbiota of the hindgut was more host-specific, while the assembly of the midgut was more influenced by the environmental microorganisms.

Eliminating a gut microbe could slash gastric cancers.

Mammoth study in Chinese villages shows antibiotics that kill Helicobacter pylori reduced cancer risk.

Immunological function of Bombyx Toll9-2 in the silkworm (Bombyx mori) larval midgut: Activation by Escherichia coli/lipopolysaccharide and regulation of growth.

Toll receptors are important regulators of insects' innate immune system which, upon binding of pathogen molecules, activate a conserved signal transduction cascade known as the Toll pathway. RNA interference (RNAi) is a powerful tool to study the function of genes via reverse genetics. However, due to the reported refractory of RNAi efficiency in lepidopteran insects, successful reports of silencing of Toll receptors in the silkworm Bombyx mori have not been reported yet. In this study, a Toll receptor of the silkworm Bombyx Toll9-2 (BmToll9-2) was cloned and its expression and function were analyzed. The results showed that BmToll9-2 contains an ectodomain (ECD) with a signal peptide and nine leucine-rich repeats, a transmembrane helix, and a cytoplasmic region with a Toll/interleukin-1 domain. Phylogenetic analysis indicates that BmToll9-2 clusters with other insect Toll9 receptors and mammalian Toll-like receptor 4. Oral infection of exogenous pathogens showed that the Gram-negative bacterium Escherichia coli and its main cell wall component lipopolysaccharide (LPS), as well as the Gram-positive bacterium Staphylococcus aureus and its main cell wall component peptidoglycan, significantly induce BmToll9-2 expression in vivo. LPS also induced the expression of BmToll9-2 in BmN4 cells in vitro. These observations indicate its role as a sensor in the innate immunity to exogenous pathogens and as a pathogen-associated receptor that is responsive to LPS. RNAi of BmToll9-2 was effective in the midgut and epidermis. RNAi-mediated knock-down of BmToll9-2 reduced the weight and growth of the silkworm. Bacterial challenge following RNAi upregulated the expression of BmToll9-2 and rescued the weight differences of the silkworm, which may be related to its participation in the immune response and the regulation of the microbiota in the midgut lumen of the silkworm larvae.

Navigating commensal dysbiosis: Gastrointestinal host-pathogen interplay orchestrating opportunistic infections.

The gut commensals, which are usually symbiotic or non-harmful bacteria that live in the gastrointestinal tract, have a positive impact on the health of the host. This review, however, specifically discuss distinct conditions where commensals aid in the development of pathogenic opportunistic infections. We discuss that the categorization of gut bacteria as either pathogens or non-pathogens depends on certain circumstances, which are significantly affected by the tissue microenvironment and the dynamic host-microbe interaction. Under favorable circumstances, commensals have the ability to transform into opportunistic pathobionts by undergoing overgrowth. These conditions include changes in the host's physiology, simultaneous infection with other pathogens, effective utilization of nutrients, interactions between different species of bacteria, the formation of protective biofilms, genetic mutations that enhance pathogenicity, acquisition of genes associated with virulence, and the ability to avoid the host's immune response. These processes allow commensals to both initiate infections themselves and aid other pathogens in populating the host. This review highlights the need of having a detailed and sophisticated knowledge of the two-sided nature of gut commensals. Although commensals mostly promote health, they may also become harmful in certain changes in the environment or the body's functioning. This highlights the need of acknowledging the intricate equilibrium in interactions between hosts and microbes, which is crucial for preserving intestinal homeostasis and averting diseases. Finally, we also emphasize the further need of research to better understand and anticipate the behavior of gut commensals in different situations, since they play a crucial and varied role in human health and disease.

The highly differentiated gut of Pachnoda marginata hosts sequential microbiomes: microbial ecology and potential applications.

Insect gut microbiomes play a crucial role in the insect development and are shaped, among other factors, by the specialized insect diet habits as well as the morphological structure of the gut. Rose chafers (Pachnoda spp.; Coleoptera: Scarabaeidae) have a highly differentiated gut characterized by a pronounced hindgut dilation which resembles a miniaturized rumen. Specifically, the species Pachnoda marginata has not been previously studied in detail in terms of microbial ecology. Here, we show a fine scale study of the highly compartmentalized gut of P. marginata by using amplicon and metagenomic sequencing to shed light on the bacterial, archaeal and fungal communities thriving in each section of the gut. We found a microbial gradient along the gut from aerobic (foregut) to strictly anaerobic communities (hindgut). In addition, we have characterized interesting biological activities and metabolic pathways of gut microbial communities related to cellulose degradation, methane production and sulfate reduction. Taken together, our results reveal the highly diverse microbial community and the potential of P. marginata gut as a source of industrially relevant microbial diversity.

Protective Effects of Laminaria japonica Polysaccharide Composite Microcapsules on the Survival of Lactobacillus plantarum during Simulated Gastrointestinal Digestion and Heat Treatment.

To improve probiotics' survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of SC/GE microcapsules, and the addition of LJP may improve thermal stability. Zeta potential measurements indicated that, at low pH of the gastric fluid, the negatively charged LJP attracted the positively charged SC/GE, helping to maintain an intact microstructure without disintegration. The encapsulation efficiency of L. plantarum-loaded LJP/SC/GE microcapsules reached about 93.4%, and the survival rate was 46.9% in simulated gastric fluid (SGF) for 2 h and 96.0% in simulated intestinal fluid (SIF) for 2 h. In vitro release experiments showed that the LJP/SC/GE microcapsules could protect the viability of L. plantarum in SGF and release probiotics slowly in SIF. The cell survival of LJP/SC/GE microcapsules was significantly improved during the heat treatment compared to SC/GE microcapsules and free cells. LJP/SC/GE microcapsules can increase the survival of L. plantarum by maintaining the lactate dehydrogenase and Na+-K+-ATPase activity. Overall, this study demonstrates the great potential of LJP/SC/GE microcapsules to protect and deliver probiotics in food and pharmaceutical systems.

Selective in vitro Synergistic Evaluation of Probiotic Tolerant morpholinyl- and 4-ethylpiperazinyl-Imidazole-chalcone Derivatives on Gastrointestinal System Pathogens.

Imidazole-chalcone compounds are recognised for their broad-spectrum antimicrobial properties. Probiotic-friendly, selective new-generation antimicrobials prove to be more efficient in combating gastrointestinal system pathogens. The aim of this study is to identify imidazole-chalcone derivatives that probiotics tolerate and evaluate their in vitro synergistic antimicrobial effects on pathogens. In this study, fifteen previously identified imidazole-chalcone derivatives were analyzed for their in vitro antimicrobial properties against gastrointestinal microorganisms. Initially, the antimicrobial activity of pathogens was measured using the agar well diffusion method, while the susceptibility of probiotics was determined by microdilution. The chosen imidazole-chalcone derivatives were assessed for synergistic effects using the checkerboard method. Four imidazole-chalcone derivatives to which probiotic bacteria were tolerant exhibited antibacterial and antifungal activity against the human pathogens tested. To our knowledge, this study is the first to reveal the fractional inhibitory concentration (FIC) of combinations of imidazole-chalcone derivatives. Indeed, the minimum inhibitory concentrations (MIC) for morpholinyl- (ZDO-3f) and 4-ethylpiperazinyl- (ZDO-3 m) imidazole-chalcones were notably low when tested against E. coli and B. subtilis, with values of 31.25 µg/mL and 125 µg/mL, respectively. The combination of morpholinyl- and 4-ethylpiperazinyl derivatives demonstrated an indifferent effect against E. coli, but an additive effect was observed for B. subtilis. Additionally, it was observed that imidazole-chalcone derivatives did not exhibit any inhibitory effects on probiotic organisms like Lactobacillus fermentum (CECT-5716), Lactobacillus rhamnosus (GG), and Lactobacillus casei (RSSK-591). This study demonstrates that imidazole-chalcone derivatives that are well tolerated by probiotics can potentially exert a synergistic effect against gastrointestinal system pathogens.

Correlation between Alzheimer's Disease and Gastrointestinal Tract Disorders.

Alzheimer's disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-ß in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer's disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.

Breathe and bloom: Gut hypoxia limits C. albicans growth.

Multiple host and microbial factors dictate whether Candida albicans can colonize the mammalian gastrointestinal tract. In this issue of Cell Host & Microbe, Savage et al. demonstrate that restoration of intestinal epithelial hypoxia is sufficient to restore Candida albicans colonization resistance, even when other Candida inhibitory effectors remain depleted.

Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering.

BACKGROUND: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). RESULTS: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. CONCLUSIONS: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

[Research progress on the characteristics of gut microbiome in early life and its influence on atopic march].

Allergic diseases are affected by both genetic background and environmental factors.In recent years, many studies have shown that allergic diseases are closely related to the gut microbiome.This article will elaborate on the composition of gut microbiome in early life and its relationship with allergies, the mechanism of action, and the influence of gut microbiome colonization on the atopic march, in order to improve the understanding of the relationship between allergy prevention or treatment and gut microbiome in children, and provide new ideas for the early prevention of allergic diseases and the early intervention of allergic processes.

Bacterial supplementation in mitigation of radiation-induced gastrointestinal damage.

Pelvic irradiation, a crucial treatment for pelvic malignancies, is associated with the risk of gastrointestinal (GI) damage due to the high proliferation rate of epithelial cells. The radiosensitive gastrointestinal tract acts as a dose-limiting organ. High doses of ionizing radiation can cause inflammation and rupture of mucosal barriers and can also lead to intestinal fibrosis. Intestinal damage can cause acute to chronic complications, reducing patients' quality of life. The gut microbiota plays a vital role in maintaining gut health, and any changes in the gut microbial composition can worsen damage, emphasizing the importance of therapies that target and sustain the gut microbiota during radiotherapy. One potential strategy to prevent radiation-induced GI damage is to use bacterial supplements. Research suggests that probiotic supplementation may alleviate radiation-induced gastrointestinal damage, maintaining intestinal morphology and decreasing epithelial injury in cancer patients. The observed protective effects occur through various mechanisms, including antioxidant activities, modulation of the immune response, and preservation of gut barrier function. To optimize probiotic therapies, it is imperative to elucidate these mechanisms. The efficiency of probiotics as radioprotectors is highly dependent on the time and dose of administration, and their interaction with the host immune system is a key facet of their therapeutic potential. This review explores the potential benefits of bacterial supplementation in mitigating radiation-induced GI damage and the underlying mechanism. This highlights the need for further research to establish standardized protocols and refine probiotic supplementation strategies, underscoring the potential for enhancing therapeutic outcomes in patients undergoing pelvic radiotherapy.

The gut microbiome in disorders of gut-brain interaction.

Functional gastrointestinal disorders (FGIDs), chronic disorders characterized by either abdominal pain, altered intestinal motility, or their combination, have a worldwide prevalence of more than 40% and impose a high socioeconomic burden with a significant decline in quality of life. Recently, FGIDs have been reclassified as disorders of gut-brain interaction (DGBI), reflecting the key role of the gut-brain bidirectional communication in these disorders and their impact on psychological comorbidities. Although, during the past decades, the field of DGBIs has advanced significantly, the molecular mechanisms underlying DGBIs pathogenesis and pathophysiology, and the role of the gut microbiome in these processes are not fully understood. This review aims to discuss the latest body of literature on the complex microbiota-gut-brain interactions and their implications in the pathogenesis of DGBIs. A better understanding of the existing communication pathways between the gut microbiome and the brain holds promise in developing effective therapeutic interventions for DGBIs.

Interaction between bacterial microbiota and nematode parasite communities in sheep's gastrointestinal tract.

The economic impact of gastrointestinal (GI) nematode infections on livestock production is well documented worldwide. Increasing evidence supports the hypothesis that parasite colonization induces significant changes in the GI tract environment and, therefore, in the landscape where the microbiota and parasites occur. Understanding the interactions between bacterial and parasite populations in the digestive tract of livestock may be useful to design parasite control strategies based on microbiota modification. The aims of this work were to investigate the impact of the oxytetracycline-mediated manipulation of the gut microbial community on the composition of GI nematode populations in naturally infected sheep and to explore changes in the GI microbial communities after nematode population treatment with the anthelmintic compound monepantel. Extensive manipulation of the GI microbiota with a therapeutic dose of the long-acting oxytetracycline formulation did not induce significant changes in the GI nematode burden. The gut microbiota of treated animals returned to control levels 17 days after treatment, suggesting strong resilience of the sheep microbial community to antibiotic-mediated microbiota perturbation. A significant decrease of the bacterial Mycoplasmataceae family (Log2FC = -4, Padj = 0.001) and a marked increase of the Methanobacteriaceae family (Log2FC = 2.9, Padj = 0.018) were observed in the abomasum of sheep receiving the monepantel treatment. While a comprehensive evaluation of the interactions among GI mycoplasma, methanobacteria and nematode populations deserves further assessment, the bacteria-nematode population interactions should be included in future control programs in livestock production. Understanding how bacteria and parasites may influence each other in the GI tract environment may substantially contribute to the knowledge of the role of microbiota composition in nematode parasite establishment and the role of the parasites in the microbiota composition.

Aedes albopictus saliva contains a richer microbial community than the midgut.

BACKGROUND: Past findings demonstrate that arthropods can egest midgut microbiota into the host skin leading to dual colonization of the vertebrate host with pathogens and saliva microbiome. A knowledge gap exists on how the saliva microbiome interacts with the pathogen in the saliva. To fill this gap, we need to first define the microbial composition of mosquito saliva. METHODS: The current study aimed at analyzing and comparing the microbial profile of Aedes albopictus saliva and midgut as well as assessing the impact of Zika virus (ZIKV) infection on the midgut and saliva microbial composition. Colony-reared Ae. albopictus strains were either exposed to ZIKV infectious or noninfectious bloodmeal. At 14 ays postinfection, the 16S V3-V4 hypervariable rRNA region was amplified from midgut and saliva samples and sequenced on an Illumina MiSeq platform. The relative abundance and diversity of midgut and saliva microbial taxa were assessed. RESULTS: We observed a richer microbial community in the saliva compared with the midgut, yet some of the microbial taxa were common in the midgut and saliva. ZIKV infection did not impact the microbial diversity of midgut or saliva. Further, we identified Elizabethkingia spp. in the Ae. albopictus saliva. CONCLUSIONS: This study provides insights into the microbial community of the Ae. albopictus saliva as well as the influence of ZIKV infection on the microbial composition of its midgut and saliva. The identification of Elizabethkingia spp., an emerging pathogen of global health significance, in Ae. albopictus saliva is of medical importance. Future studies to assess the interactions between Ae. albopictus saliva microbiome and ZIKV could lead to novel strategies for developing transmission barrier tools.

Epidemiology and multiple colonization of gastrointestinal pathogens in rural Tanzanian children with and without diarrhea: A case-control study.

Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.

Microfluidic Strategies for Encapsulation, Protection, and Controlled Delivery of Probiotics.

Probiotics are indispensable for maintaining the structure of gut microbiota and promoting human health, yet their survivability is frequently compromised by environmental stressors such as temperature fluctuations, pH variations, and mechanical agitation. In response to these challenges, microfluidic technology emerges as a promising avenue. This comprehensive review delves into the utilization of microfluidic technology for the encapsulation and delivery of probiotics within the gastrointestinal tract, with a focus on mitigating obstacles associated with probiotic viability. Initially, it elucidates the design and application of microfluidic devices, providing a precise platform for probiotic encapsulation. Moreover, it scrutinizes the utilization of carriers fabricated through microfluidic devices, including emulsions, microspheres, gels, and nanofibers, with the intent of bolstering probiotic stability. Subsequently, the review assesses the efficacy of encapsulation methodologies through in vitro gastrointestinal simulations and in vivo experimentation, underscoring the potential of microfluidic technology in amplifying probiotic delivery efficiency and health outcomes. In sum, microfluidic technology represents a pioneering approach to probiotic stabilization, offering avenues to cater to consumer preferences for a diverse array of functional food options.

Peyer's Patch: Possible target for modulating the Gut-Brain-Axis through microbiota.

The gastrointestinal (GI) tract and the brain form bidirectional nervous, immune, and endocrine communications known as the gut-brain axis. Several factors can affect this axis; among them, various studies have focused on the microbiota and imply that alterations in microbiota combinations can influence both the brain and GI. Also, many studies have shown that the immune system has a vital role in varying gut microbiota combinations. In the current paper, we will review the multidirectional effects of gut microbiota, immune system, and nervous system on each other. Specifically, this review mainly focuses on the impact of Peyer's patches as a critical component of the gut immune system on the gut-brain axis through affecting the gut's microbial composition. In this way, some factors were discussed as proposed elements of missing gaps in this field.