Pharmacomicrobiomics in Psoriasis: Microbiome-Drug Interactions Across Systemic Treatments.

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.

Impact of antibiotic therapy on cutaneous and gut microbiota in Rana dybowskii amphibians: Insights and implications

TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis

Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don't respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.

BackgroundThe gut microbiome has been associated with response to anti-PD-1 therapy in melanoma, lung cancer, and kidney cancer. Small clinical trials combining gut microbiome modulation via fecal microbiota transplantation (FMT)...

Mode of delivery has an impact on the gut microbiota of newborn infants. It has been reported that infants delivered by Caesarean section (C-section) typically have a lack of Bacteroides species and delayed Bifidobacterium development in the gut microbiota when compared with those delivered vaginally.1 Epidemiologic data have indicated that that C-sections are associated with chronic immune system-related diseases, such as rheumatoid arthritis and type I diabetes.2 It is possible that this association is partly formed in the interaction of the host and the different gut microbiota of infants delivered by C-section.3 Previous attempts to correct the microbiota of infants delivered by C-section have included oral administration of vaginal flora to the newborn infant and probiotic supplements, including Bifidobacteria. However, the impact of these interventions has been limited.4, 5 The gut microbiota of newborn infants who are born vaginally are colonised by maternal gut bacteria. That is why we studied whether a faecal transplant from mothers to newborn infants delivered by C-section would correct the imbalance caused by this mode of delivery.6, 7 We carried out a proof of principle and safety trial and recruited 17 pregnant women aged 31–40 who were scheduled for an elective C-section. After careful screening for potential pathogens, seven of these expectant mothers were selected for a faecal transplant once their infants were born. A faecal sample was obtained two weeks before their planned C-section and prepared for transplantation. The infants, five girls and two boys, received a small amount of faecal transplant from their mothers, namely 3.5–7 mg, which was mixed with their mother's milk when they were first fed within two hours of delivery.7 The infants, who were all born at 37 weeks ± 3 days and weighed 2861–3528 grams, were followed up for three months, and there were no clinical symptoms association with the transplantation. Repeated faecal sampling from the infants that we treated showed that the composition of their faecal microbiota was strikingly similar to the faecal microbiota samples previously collected from vaginally delivered infants. In particular, the lack of Bacteroides species and Bifidobacterium that are typically observed in infants delivered by C-section were corrected. Moreover, the microbiome of both the vaginally born infants, and those born by C-section and given faecal transplants, showed mark differences to infants who were previously given maternal vaginal flora.7 Our study demonstrates that the intestinal microbiota of infants delivered by C-section can be successfully normalised by maternal faecal microbiota transplants. However, the prerequisites for this method are meticulous screening of the mother and careful follow-up of the newborn infant. To assess the long-term effects of faecal transplants on the intestinal flora, and the growth and development of newborn infants, we are currently performing a larger randomised controlled trial on infants delivered by C-section. The trial will also enable us to study the interactions between the intestinal microbiome and the early development of the immune system, which may generate new data on the origins of atopic and autoimmune diseases. Future studies are required to show whether providing infants born by C-section with faecal transplants could become part of clinical routines. At the moment, it is important that faecal transplants should only be performed as part of research projects and that they should include rigorous clinical and microbiological screening and follow-ups. The authors have no conflicts of interest to declare.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes serious intensive care unit (ICU)-acquired infections, yet the mechanisms of microbiota-mediated colonization resistance remain unclear. We analyzed the gut microbiome and metabolic profiles of healthy individuals and ICU patients, distinguishing those with and without CRKP colonization. ICU patients showed distinct microbial communities compared to healthy controls, and CRKP-positive patients exhibited unique microbial and metabolic signatures. We demonstrated that a healthy gut microbiome is essential for providing resistance against CRKP colonization in antibiotic-perturbed mouse with fecal microbiota transplantation (FMT). Both in vitro and in vivo experiments revealed that Lactiplantibacillus plantarum and Bifidobacterium longum as significant contributors to the decolonization of CRKP. Furthermore, we showed that probiotic supplementation or FMT significantly improved CRKP colonization resistance. The findings highlight that a specific gut microbiome is essential for resisting CRKP colonization, and that targeted microbiome restoration may serve as a viable strategy to prevent CRKP colonization in ICU patients.

BackgroundSkin lesions can occur during the progression of pancreatic cancer. With growing attention on the gut-skin axis, these lesions may be linked to the microbiota. Microbiota play a crucial role in skin-related conditions, including hair loss and overall skin health. However, few studies have investigated the dynamic changes in gut and skin microbiota associated with skin lesions during cancer progression. In this study, 16S rRNA gene sequencing was used to investigate the dynamic changes of the gut microbiota in mice without non-depilation (Unepi) and depilation (Epi) after PAN02 cell injection. We also revealed the changes in skin microbiota of Unepi mice (Unepi_D) and Epi mice (Epi_D) after depilation.ResultsOur study found that the alpha diversity significantly increased in Unepi_D, indicating an imbalance in gut microbiota homeostasis. In the skin microbiota, certain genera such as Staphylococcus and Devosia were up-regulated, while others like Lactobacillus were down-regulated. Similarly, in the gut microbiota, Parasutterella was enriched, whereas Blautia showed reduced abundance. In the Epi group, the trend of increasing pathogenic bacteria and decreasing probiotics suggests a disrupted microbial environment that may contribute to skin injury through the gut–skin axis. These findings highlight potential microbial targets for diagnosis and therapeutic intervention in pancreatic cancer-associated skin complications.ConclusionTherefore, our findings provide new insights and references for the prevention and treatment of skin-related diseases in clinical practice. Specific gut and skin microbiota alterations may serve as potential biomarkers or therapeutic targets for managing skin complications in pancreatic cancer patients.Clinical trial numberNot applicable.

Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.

Given the impact of the gut microbiome on human physiology and aging, it is possible that the gut microbiome may affect locomotion in the same way as the host’s own genes. There is not yet any direct evidence linking the gut microbiome to locomotion, though there are some potential connections, such as regular physical activity and the immune system. In this study, we demonstrate that the gut microbiome can contribute differently to locomotion. We remodeled the original gut microbiome of mice through fecal microbiota transplantation (FMT) using human feces and compared the changes in locomotion of the same mice before and three months after FMT. We found that FMT affected locomotion in three different ways: positive, none (the same), and negative. Analysis of the phylogenesis, α-diversities, and β-diversities of the gut microbiome in the three groups showed that a more diverse group of intestinal microbes was established after FMT in each of the three groups, indicating that the human gut microbiome is more diverse than that of mice. The FMT-remodeled gut microbiome in each group was also different from each other. Fold change and linear correlation analyses identified Lacrimispora indolis, Pseudoflavonifractor phocaeensis, and Alistipes senegalensis in the gut microbiome as positive contributors to locomotion, while Sphingobacterium cibi, Prevotellamassilia timonensis, Parasutterella excrementihominis, Faecalibaculum rodentium, and Muribaculum intestinale were found to have negative effects. This study not only confirms the presence of gut microbiomes that contribute differently to locomotion, but also explains the mixed results in research on the association between the gut microbiome and locomotion.

BACKGROUNDEmerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear. AIMTo evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.METHODSDextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.RESULTSCompared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1.CONCLUSIONFMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.

Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

In recent years, gastrointestinal microbiota and fecal microbiota transplantation (FMT) has gained rapidly development.The recent studies demonstrated that FMT has obvious clinical efficacy and safety on the treatment of clostridium difficile infection, inflammatory bowel disease and other diseases in adult.The present article will discuss the efficacy of FMT in treating digestive diseases in children.This review summarizes therapeutic advances in FMT, latest FMT therapies and presents the potential of FMT therapeutics in gastrointestinal and extra-intestinal conditions in children. Key words: Fecal microbiota transplantation; Gastrointestinal microbiota; Child

The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.