Psoriasis and Gut Microbiome—Current State of Art

Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The “leaky gut syndrome” and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.     

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.     

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.     

Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macrophages and 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 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 highlights the time-dependent transformation of reactive microglia and astrocytes into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide suggestions on how to modulate the inflammation and discuss key therapeutic approaches leading to better functional outcome after SCI.     

Intratracheal Transplantation of Mesenchymal Stem Cells Attenuates Hyperoxia-Induced Microbial Dysbiosis in the Lungs,Brain, and Gut in Newborn Rats

We attempted to determine whether intratracheal (IT) transplantation of mesenchymal stem cells (MSCs) could simultaneously attenuate hyperoxia-induced lung injuries and microbial dysbiosis of the lungs, brain, and gut in newborn rats. Newborn rats were exposed to hyperoxia (90% oxygen) for 14 days. Human umbilical cord blood-derived MSCs (5 × 10⁵) were transplanted via the IT route on postnatal day (P) five. At P14, the lungs were harvested for histological, biochemical, and microbiome analyses. Bacterial 16S ribosomal RNA genes from the lungs, brain, and large intestine were amplified, pyrosequenced, and analyzed. IT transplantation of MSCs simultaneously attenuated hyperoxia-induced lung inflammation and the ensuing injuries, as well as the dysbiosis of the lungs, brain, and gut. In correlation analyses, lung interleukin-6 (IL-6) levels were significantly positively correlated with the abundance of Proteobacteria in the lungs, brain, and gut, and it was significantly inversely correlated with the abundance of Firmicutes in the gut and lungs and that of Bacteroidetes in the lungs. In conclusion, microbial dysbiosis in the lungs, brain, and gut does not cause but is caused by hyperoxic lung inflammation and ensuing injuries, and IT transplantation of MSCs attenuates dysbiosis in the lungs, brain, and gut, primarily by their anti-oxidative and anti-inflammatory effects.     

Fecal Microbiota Transplantation Derived from Alzheimer’s Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer’s disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus Muribaculum and a decrease in Lactobacillus johnsonii compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.     

Chronic-Antibiotics Induced Gut Microbiota Dysbiosis Rescues Memory Impairment and Reduces β-Amyloid Aggregation in a Preclinical Alzheimer’s Disease Model

Alzheimer’s disease (AD) is a multifactorial pathology characterized by β-amyloid (Aβ) deposits, Tau hyperphosphorylation, neuroinflammatory response, and cognitive deficit. Changes in the bacterial gut microbiota (BGM) have been reported as a possible etiological factor of AD. We assessed in offspring (F1) 3xTg, the effect of BGM dysbiosisdysbiosis in mothers (F0) at gestation and F1 from lactation up to the age of 5 months on Aβ and Tau levels in the hippocampus, as well as on spatial memory at the early symptomatic stage of AD. We found that BGM dysbiosisdysbiosis with antibiotics (Abx) treatment in F0 was vertically transferred to their F1 3xTg mice, as observed on postnatal day (PD) 30 and 150. On PD150, we observed a delay in spatial memory impairment and Aβ deposits, but not in Tau and pTau protein in the hippocampus at the early symptomatic stage of AD. These effects are correlated with relative abundance of bacteria and alpha diversity, and are specific to bacterial consortia. Our results suggest that this specific BGM could reduce neuroinflammatory responses related to cerebral amyloidosis and cognitive deficit and activate metabolic pathways associated with the biosynthesis of triggering or protective molecules for AD.