White adipose tissue (WAT) and gut are involved as inducers of neuroinflammation when they detect injury and trigger inflammation. The autonomous nervous system innervates both tissues, although the roles of the sympathetic, parasympathetic and enteric nervous systems have not been fully elucidated. Here, we revisited the participation of both types of inflamed peripheral tissue in neuroinflammation. We first analyzed how inflamed peripheral WAT plays a key role in neuroinflammation once metainflammation is installed. Second, we described the impact of insulin resistance (IR) on hypothalamic dysfunction, T2DM and neurodegenerative diseases. Finally, we analyzed the gut-brain axis, examining cell interactions, soluble factors, the sensing of microbes and the role of the intestinal microbiota and mucosal barriers in neuroinflammation. Since intestinal mucosa and secondary lymphoid organs are densely innervated by the sympathetic, parasympathetic, and enteric nervous systems, we analyzed bidirectional crosstalk between different tissues, neurons, and immune systems in healthy and pathological circumstances to restore normal tissues functions, and consequently homeostasis.

Maternal gut and breast milk (BM) are key in vertically transmission bacteria to infants, shaping their gut microbiota in early life. Although the establishment of early gut microbiota is known, the role of the combined influence of maternal factors and newborn characteristics are not explored. In this study we aimed to assess the influence of maternal BMI and total body fat, age, delivery mode, and newborn sex on the diversity and composition of the BM and gut microbiota (GM) in mother- newborn dyads. In this cross-sectional study, of the 986 pregnant women candidates, 53 participated, and finally, 40 mother-newborn dyads exclusively breastfeeding at 20-28 days post-partum were included. Metataxonomic profiling of DNA extracted from BM and fecal samples was conducted using 16S rRNA sequencing. Globally, the findings offer valuable insights that excessive adiposity, age and C-section delivery influence on a lower abundance of specific taxa in the BM, maternal gut, and gut newborns. Also, the simultaneous analysis of maternal factors and newborn characteristics shows that maternal age and newborn sex explain an important variation in the microbiota composition. These results add to understanding of the intricate interplay between maternal factors and the microbial communities that influence early-life gut and BM microbiota.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

Administration of crude polysaccharides extract from natural product is a promising gut microbiota-targeted approach to preventing obesity and associated metabolic disorders. Dietary restrictions can change the type and number of gut bacteria, which is an important factor in delaying the onset and burden of diseases. This study aimed to investigate the effects of high-yield crude polysaccharides from Cordyceps militaris (CMP) on high-fat diet (HFD) mice model and the gut microbiota community assembly, and to identify whether selenium (Se) addition would improve CMP action mode during cultivation. We found that the CMP treatment ameliorated adipose and liver pathologic morphology and fat accumulation in obese mice, while, SeCMP intervention was not superior than CMP in body mass gain, but notably decreasing serum triglyceride level increased by HFD. The upregulated expression of gene Cyp7a1 in liver and protein UCP1 in brown adipose tissue (BAT) preliminary indicated that the effect might relate to bile acids (BAs) metabolism pathway and thermogenesis. In addition, CMP showed a drastic decrease in the gut microbes which positively correlated with dyslipidemia parameters. Our result reveals the potential of CMP to be used as functional food in the prevention of diet-induced adipose and liver steatosis, so does SeCMP has outstanding capacity of improving dyslipidemia.

Fucoidans, known for their diverse biological properties such as anti-inflammatory, antiviral, antitumor, and immune-stimulatory effects, have recently gained attention for their potential benefits in exercise endurance, muscle mass, and anti-fatigue. However, the mechanisms by which fucoidans enhance exercise performance are still unclear. To investigate these effects, we administered 400 mg/kg/day of fucoidan extract derived from Undaria pinnatifida to sixty-four C57BL/6J mice over ten weeks. We evaluated changes in running activity, mitochondrial-related gene expression in skeletal muscle, and alterations in the intestinal microbiome. Our results showed that fucoidan supplementation significantly increased daily running distance and muscle mass by 25.5% and 10.4%, respectively, in mice on a standard chow diet, and with more modest effects observed in those on a high-fat diet (HFD). Additionally, fucoidan supplementation led to a significant increase in beneficial gut bacteria, including Bacteroides/Prevotella, Akkermansia muciniphila, and Lactobacillus, along with a notable reduction in the Firmicutes/Bacteroidetes ratio, indicating improved gut microbiome health. Mechanistically, fucoidan supplementation upregulated the mRNA expression of key genes related to mitochondrial biogenesis and oxidative capacity, such as COX4, MYH1, PGC-1α, PPAR-γ, and IGF1, in both standard chow and HFD-fed mice. Our findings suggest that fucoidan supplementation enhances exercise performance, improves muscle function, and positively modulates the gut microbiome in mice, regardless of diet. These effects may be attributed to fucoidans' potential prebiotic role, promoting the abundance of beneficial gut bacteria and contributing to enhanced exercise performance, increased muscle strength, and improved recovery.

The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds of millions of years. Over the past decade, a growing body of knowledge has underscored the intricate connections among diet, gut microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, sea-weeds, and fungi have diverse biological functions, including antioxidant, immunoregulatory, and metabolic activities. Their effects are closely tied to the gut microbiota, which metabolizes BPs into health-influencing compounds. Understanding how BPs and gut microbiota interact is critical for harnessing their potential health benefits. This review provides an overview of the human gut microbiota, focusing on its role in metabolic diseases like obesity, type II diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). It explores the basic characteristics of several BPs and their impact on gut microbiota. Given their significance for human health, we summarize the biological functions of these BPs, particularly in terms of im-munoregulatory activities, blood sugar, and hypolipidemic effect, providing a valuable reference for understanding the potential benefits of natural BPs in treating metabolic diseases. These properties make BPs promising agents for preventing and treating metabolic diseases. The comprehensive understanding of the mechanisms by which BPs exert their effects through gut microbiota opens new avenues for developing targeted therapies to improve metabolic health.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

Background: Bacteria, among the earliest life forms on Earth, are integral to both human health and environmental ecosystems. They contribute to essential processes such as digestion, nutrient absorption, and immune defense, and play key roles in the biogeochemical cycles that sustain life. Objective: This paper explores the indispensable role of bacteria in human life and environmental health, emphasizing their contributions to digestion, nutrient absorption, immune protection, and ecosystem functioning. It also discusses advances in understanding the human microbiome and their implications for health and therapeutic interventions. Methods: The study reviews existing literature on the human microbiome, probiotics, and the role of bacteria in environmental nutrient cycling. It analyses experimental evidence and case studies, particularly focusing on the impact of fecal microbiota transplantation (FMT) as a therapeutic tool. Metagenomic analysis techniques are examined to highlight the diversity and functionality of gut bacteria. Results: Bacteria are found to be essential for breaking down food, providing vital nutrients, and protecting against pathogens. They play a critical role in maintaining a healthy immune system and are involved in the biogeochemical cycles necessary for ecosystem health. Metagenomic analysis reveals significant variations in bacterial populations associated with health and disease, emphasizing the importance of a balanced microbiota. FMT shows promise as an effective treatment for various diseases, including gastrointestinal, metabolic, and neurological disorders. Conclusions: Bacteria are crucial for human health and environmental stability. Maintaining a balanced microbiota is vital for overall well-being, and interventions such as probiotics and FMT can offer significant health benefits. Future research should focus on further understanding the complex interactions between bacteria and their hosts to develop targeted therapies for various health conditions.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and down-regulating the canonical Wnt / β-catenin pathway. Further, PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated ‎with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently ‎linking them to CRC and mapping them against UniprotKB and GO databases for specific ar-‎chaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in ‎healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. ‎Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, ‎Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus ‎Mancarchaeum acidiphilum, Natrinema sp. J7-2 and Ferroglobus placidus emerge as potential archaeal ‎biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC ‎dynamics.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

Carrot juice and its associated beverage products are well-known healthy drinks all over the world. However, what effect carrot juice has on the human gut microbiota and how it is fermented by the intestinal microbes have not been studied. Here, using an in vitro model of anaerobic fermentation, we demonstrated that carrot juice could be fermented into lactate and acetate by the human gut microbiota. 16S high-throughput sequencing and bioinformatic analyses indicated that fermentation of carrot juice could significantly change the composition of the human gut microbiome. Interestingly, carrot juice remarkably increased the abundances of beneficial bacteria, including Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus mucosae and Bacteroides uniformis and decreased the population of opportunistic pathogenic bacteria, such as Enterococcus faecium in the gut. Collectively, our study illustrates a favorable effect of carrot juice on the human gut microbiota and lays a foundation for the development of carrot juice as a novel prebiotic agent.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general progress of emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), where the ischemic segments of the intestine were examined. Nine others were operated for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT image of non-ischemic (control group), viable ischemic and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

(1) Background: Considering the autoimmune nature with genetic predisposition of alopecia areata, and the immunomodulatory properties of some probiotics, the present study was conducted in patients with alopecia areata. (2) Method: A 24-weeks randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of an oral probiotic intake in severity of alopecia areata and the effect on skin and gut microbiota. 3) Results: The number of alopecia areata plaques decresed in 56% of patients in the probiotic group vs. 30% in the placebo group. Patients with improvement on the affected skin surface area, showed a results of 45% and 20% in probiotic and placebo groups, respectively. For "activity", "inactivity” and "regrowth", an improvement in 55%, 67% and 55% of patients was respectively observed in the probiotic group, compared to 50%, 40% and 30% in the placebo group. No changes were observed in the gut microbiota during the intervention period. Regarding skin microbiota, changes were detected in the probiotic group, with reductions in characteristic genera during the study. (4) Conclusions: To our knowledge, this is the first clinical trial assessing the efficacy of a probiotic in patients with alopecia areata. This probiotic mixture improves the course and modify the skin microbiota of these patients.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

Three different fields intersect in search of an understanding of the point-of-origin of modern-age diseases: 1) D-amino acids and their role under stress conditions; 2) evolutionary origin of the mitochondrion organelle in the eukaryotic cell; and 3) gut microbiota and human healthHere it is first suggested that D-amino acids function as universal signaling agents, after having evolved as prokaryotic communication, part of an organic communication process that governs the basic activities of all the cells and coordinates cell action.Mitochondria (symbiotic prokaryotic organelles), are creative source of D-amino acids as signaling agents in the central nervous system and in the neuroendocrine systems.Amino acids racemases catalyzes the conversion between the L-enantiomers ( protein building blocks) into D-enantiomers (signaling agents).It is suggested that hectic modern life may affect human health by causing stress to the gut microbiota. These affected, gut microbiota then secrete D-amino acids that enter the blood stream, as signaling agents, causing communication errors in the central nervous system, and in the neuroendocrine systems due to excessive quantity of D-amino acids.Treating gut microbiota with inhibitors of amino acids racemases or finding D-amino acid scavengers may be used in developing novel therapeutic strategies for diseases related to the central nervous system and neuroendocrine systems caused by stressed gut microbiota.

About 10% of angiosperms, an estimated 20,000 species, produce latex from ubiquitous isoprene precursors. Latex, an aqueous suspension of rubber particles and other compounds, functions as an antifeedant and herbivory deterrent. Here, I propose that the solubility of latex in neutral to alkaline pH supports the hypothesis that foregut-fermenting herbivores such as ruminants, kangaroos, sloths, insect larvae and tadpoles have evolved to adapt to the ingestion of latex with the evolution of alkaline anterior digestive chamber(s). However, they consequently become susceptible to the action of Bacillus thuringiensis (Bt) -endotoxin and related bioinsecticides which are activated in alkaline environments. By contrast, hindgut-fermenting herbivores such as horses and rabbits have acidic anterior digestive chambers in which latex coagulates and may cause gut blockage, but in which Bt is not activated. The latex-adapted foregut herbivore vs. latex-maladapted hindgut herbivore hypothesis developed in this paper has implications for foregut-fermenting husbanded livestock and zoo animals which may be provided with latex-containing forage that is detrimental to their gut health. Further, ruminants and herbivorous tadpoles with alkaline anterior chambers are at risk for damage by the supposedly “environmentally-friendly” Bt bioinsecticide which is widely disseminated, or engineered into crops which may enter animal feed streams.

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

The present study examined metabolites in Northern wild rice (WLD), the impact of WLD supplemented high fat (HF) diet on gut microbiota, short chain fatty acids (SCFAs) and correlation with metabolism or inflammation versus HF+white rice (WHR) in mice. C57BL/6J mice received HF diet supplemented with 26g% WHR, 26g% WLD, or 13g% WHR+13g% WLD (WTWD) for 12 weeks. The levels of fasting plasma glucose, total cholesterol, triglycerides, insulin resistance, inflammatory cytokines and monocyte adhesion were lower, and the abundances of fecal Lactobacillus gasseri species bacteria and propionic acid were higher in HF+WLD diet-fed mice compared to HF+WHR diet-fed mice (p<0.05). The anti-inflammatory effects of HF+WTWD diet were weaker than that in HF+WLD diet, but were greater than that in HF+WHR diet-fed mice (p<0.05). Relative abundances of fecal Lactobacillus gasseri and propionic acid in HF+WLD fed-mice were higher than that in HF+WHR fed mice. The abundance of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers (p<0.05). The findings suggest that WLD dose-dependently attenuated metabolic and inflammatory disorders in HF diet-fed mice. Interactions between WLD components and gut microbiota may upregulate fecal propionic acid and contribute to metabolic and anti-inflammatory benefits of WLD diet-induced insulin resistant mice.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.