The Association of Gut Microbiome with Anesthesia Outcomes, Pain Management, and Patient Recovery

Gut feelings-the gut microbiome as a regulator of mental health in polycystic ovary syndrome.

BackgroundThe human microbiome plays a vital role in human health, mediated by the gut–brain axis, with a large diversity of functions and physiological benefits. The dynamics and mechanisms of meditations on oral and gut microbiome modulations are not well understood. This study investigates the short-term modulations of the gut and oral microbiome during an Arhatic Yoga meditation retreat as well as on the role of microbiome in improving well-being through a possible gut-brain axis.MethodsA single-arm pilot clinical trial was conducted in a controlled environment during a 9-day intensive retreat of Arhatic Yoga meditation practices with vegetarian diet. Oral and fecal samples of 24 practitioners were collected at the start (Day0: T1), middle (Day3: T2), and end (Day9:T3) of the retreat. Targeted 16S rRNA gene amplicon sequencing was performed for both oral and gut samples. Functional pathway predictions was identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). DESeq2 was used to identify the differential abundant taxa. Various statistical analyses were performed to assess the significant changes in the data.ResultsOur findings revealed that Arhatic Yoga meditation together with a vegetarian diet led to changes in the oral and gut microbiome profiles within the 9-day retreat. Oral microbiome profile showed a significant (p < 0.05) difference in the species richness and evenness at the end of study, while non-metric multidimensional scaling (NMDS) confirmed the shift in the gut microbiome profile of the practitioners by T2 timepoint, which was further supported by PERMANOVA analysis (p < 0.05). Health-benefiting microbes known to improve the gastrointestinal and gut-barrier functions, immune modulation, and gut-brain axis were enriched. Gut microbiome of both beginner and advanced Arhatic Yoga practitioners showed similar trends of convergence by the end of study. This implies a strong selection pressure by Arhatic Yoga meditation together with a vegetarian diet on the beneficial gut microbiome.ConclusionThis pilot study demonstrates that Arhatic Yoga meditation practices combined with a vegetarian diet during a short intensive retreat resulted in enrichment of known health-promoting microbes. Such microbial consortia may be developed for potential health benefits and used as probiotics to improve the gastrointestinal and immune systems, as well as functions mediated by the gut-brain axis.Trial registrationStudy was submitted in https://clinicaltrials.gov/on28-02-2024. Retrospective registered.

BackgroundGut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC).AimsTo investigate the association between gut microbiome and efficacy of ICI in patients with HCC.MethodsPatients with HCC who were scheduled to receive ICI were prospectively enrolled. Fecal samples were collected within 7 days before initiation of ICI (baseline) and 8 weeks later. Gut microbiome was assessed using 16S rRNA sequencing and shotgun whole-genome sequencing and correlated with objective response (complete or partial response), disease control (objective response or stable disease for ≥16 weeks), and overall survival.ResultsThirty-six patients with HCC were enrolled, and 20 of them provided both baseline and 8-week feces. Alpha diversity, richness, and compositions of baseline gut microbiome indicated no difference between responders and nonresponders or between disease control and nondisease control groups. For the 20 paired feces, immunotherapy did not change any of the major microbiome features. No specific taxa were enriched in patients with objective response. Three taxa—Bifidobacterium, Coprococcus, and Acidaminococcus—were enriched in patients with disease control. However, the baseline abundance of these three taxa did not predict overall survival benefit.ConclusionsIn this exploratory study, we failed to disclose any overt association of gut microbiome with the efficacy of ICI in patients with HCC. A larger prospective study is warranted for definite conclusion.

The Gut Microbiome in Health and Disease

The gut-brain axis concept has become an exciting area of research in psychiatry. Gastrointestinal inflammation and gut microbiome dysbiosis have been associated with mental health disorders. Obsessive-compulsive disorder (OCD) is a debilitating and complex mental illness that cannot be completely curable, stemming from many causes and risk factors. Generally, there is limited research on OCD and its association with the gut microbiome compared to other psychiatric conditions such as depression and anxiety. This review aims to provide insights into the association of gut microbiome and gastrointestinal inflammation with OCD. Besides, the role of probiotics as a potential therapy will be discussed in this review. The studies compiled in this review demonstrated variations in the gut microbial composition, often with lower microbial diversity in OCD patients compared to the controls. The gut microbiome is also involved in regulating the immune system. Alteration in certain groups of gut bacteria could give rise to inflammation and manifestations of gastrointestinal symptoms in OCD patients. As an approach to restoring the balance of the gut microbiome, probiotics serve as an effective solution. In vivo animal studies showed that probiotics can potentially improve OCD symptoms. Nevertheless, clinical trials are required to determine the efficacy of probiotics as an adjuvant therapy to alleviate OCD symptoms.

The gut microbiota consists of trillions of microorganisms in the digestive tract. It holds immense promise in various aspects of human health and well-being. Our understanding of its full potential is still developing. It has implications for digestive health, mental health and brain function, personalized medicine, immune system regulation, disease prevention and treatment, metabolic health, weight management, and others. Here we highlight some aspects of gut microbiota that have shown significant promise in recent research. Personalized Microbiome Medicine: Researchers have been increasingly focusing on personalized microbiome medicine. This involves understanding how an individual's unique gut microbiota composition can influence their health and disease risk. This understanding could lead to personalized dietary and therapeutic interventions based on a person's microbiome profile. Gut-Brain Axis and Mental Health: The connection between the gut and the brain, known as the gut-brain axis, has gained significant attention. Emerging research suggests that gut microbiota can influence mental health conditions such as anxiety, depression, and neurodegenerative disorders. This has led to exploring novel treatments targeting the gut microbiota to improve mental health outcomes. Microbiota Transplants: Fecal microbiota transplantation (FMT) has continued to be an area of research interest. FMT involves transferring fecal material from a healthy donor to a recipient's gut to restore a balanced microbial ecosystem. It has shown promise in treating certain gastrointestinal disorders, such as recurrent Clostridium difficile infections, and researchers are also investigating its potential for other conditions. Diet and Microbiota interaction: The impact of diet on the gut microbiota composition and its subsequent influence on health has been a focus of recent research. Studies have demonstrated how different diets, such as high-fiber diets or those rich in certain plant-based foods, can promote the growth of beneficial gut bacteria and contribute to overall well-being. Metagenomics: Advances in metagenomics and sequencing technologies have allowed researchers to study gut microbiota with higher resolution. This has enabled the identification of previously unknown microbial species and functions, leading to a deeper understanding of the complex microbial communities residing in the gut. Microbiota and Immune System: Research has shown that gut microbiota plays a crucial role in regulating the immune system. Dysbiosis, an imbalance in the gut microbiota, has been linked to various autoimmune diseases and allergic conditions. Understanding these interactions could potentially lead to innovative immune-modulating therapies. Metabolic Diseases: There's growing evidence that the gut microbiota is linked to metabolic disorders like obesity, type 2 diabetes, and metabolic syndrome. Researchers are studying how specific bacterial species and their metabolites impact metabolism and contribute to these conditions. Synthetic Microbiota and Therapeutics: Scientists are exploring the possibility of designing synthetic microbial communities (synbiotics) to target specific health outcomes. These synthetic communities could be used as therapeutic interventions for various diseases, offering a controlled and tailored approach to manipulating the gut microbiota. The future of gut microbiota research holds exciting possibilities as our understanding of the complex interactions between microbiota and human health continues to deepen. One important area to look for in the future is the application of artificial intelligence tools to gut microbiota. Applying machine learning and artificial intelligence to gut microbiota data will help identify patterns and correlations that traditional analyses may miss. These tools could aid in understanding complex microbial communities and their associations with health and disease.

The steady-state gut microbiome not only promotes the metabolism and absorption of nutrients that are difficult to digest by the host itself, but also participates in systemic metabolism. Once the dynamic balance is disturbed, the gut microbiome may lead to a variety of diseases. Recurrent pregnancy loss (RPL) affects 1-2% of women of reproductive age, and its prevalence has increased in recent years. According to the literature review, the gut microbiome is a new potential driver of the pathophysiology of recurrent abortion, and the gut microbiome has emerged as a new candidate for clinical prevention and treatment of RPL. However, few studies have concentrated on the direct correlation between RPL and the gut microbiome, and the mechanisms by which the gut microbiome influences recurrent miscarriage need further investigation. In this review, the effects of the gut microbiome on RPL were discussed and found to be associated with inflammatory response, the disruption of insulin signaling pathway and the formation of insulin resistance, maintenance of immunological tolerance at the maternal-fetal interface due to the interference with the immune imbalance of Treg/Th17 cells, and obesity.

Sir, The human body is inhabited by a multitude of bacteria, viruses, fungi, phages constituting the microbiota, and their gene pool called the microbiome which is essential for human well-being.[1] The role of gut microbiome in peri-operative medicine is recently being explored. However, most of the literature available is that of animal studies and more extensive research would be needed in humans to establish an association. The mechanism of action of gut-microbiome on various systems of the human body can be explained by the “gut-brain axis.” This is a two-way interaction between the enteric nervous system (ENS) and central nervous system (CNS) [Figure 1]. The gut microbiota secrete various metabolites and products like-short chain fatty acids (SCFA), enzymes, polysaccharides, cytokines, and neurotransmitters, which are released in to the circulation to act on the CNS. The vagus nerve also carries inputs from ENS to CNS. The brain in-turn acts on the gut through the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system.[2] Immune mediated interaction and alteration of microglial activity are other proposed mechanisms of gut-brain interaction. All these mechanisms have been proven only by preclinical animal studies.[1]Figure 1: Gut brain axis. HPA = Hypothalamic pituitary adrenal axisAnaesthetic agents-like propofol and volatile anaesthetics have been found to alter the gut microbiota composition in animal studies. Han et al. studied gut microbiota of mice after sevoflurane exposure and found that microbiome composition was reduced on day-1, 3, 7, and 14 after sevoflurane anaesthesia compared to the control group. They also noted a significant difference in fecal metabolites of the experimental and control groups.[3] Also an infusion of propofol for 3 hours in rats was found to decrease the number of certain bacterial species for 14 days.[4] Postoperative delirium (POD) and post-surgical pain (PSP) have also been attributed to the gut-microbiome by animal studies. This means, why certain patients have more POD or PSP than others can be determined by their gut-microbiome constitution and may be pre-treatment with pre-biotics, post-biotics, or fecal microbiota transplantation reduces the risk of POD and PSP in these patients. However, this association between POD/PSP and gut-microbiome has been shown mostly in animal studies and human association is yet to be established.[1] Zhang et al. compared the gut-microbiota of rats who developed POD and those who did not develop POD after abdominal surgery. The composition of microbiota was significantly different between the groups. They also conducted fecal microbiota transplantation from rats with POD to antibiotic treated rats, which then developed POD.[5] A human study has proved association of gut microbiome with chronic PSP, where Yao et al. had preoperatively collected gut-microbiome samples for 132 patients undergoing breast cancer surgery. The gut microbiota of 66 patients who developed chronic PSP (CPSP) was significantly different from those who did not develop PSP. Fecal microbiome transplantation from CPSP patients to mice led to development of hyperalgesia in these mice.[6] The gut microbiome composition has been attributed to development of opioid tolerance. Chronic opioid exposure leads to activation of opioid receptors on gut epithelium and destruction of gut mucosal barrier, allowing translocation of gut bacteria leading to an inflammatory response and pain exacerbation.[1] The gut microbiota composition influences many chronic pain conditions like fibromyalgia, headache, neuropathic, visceral, and chronic pelvic pain. The mediators of gut microbiota can alter the neuronal excitability at the dorsal root ganglia and mediate neuro inflammation leading to central sensitization and peripheral sensitization in chronic pain. Thus, targeting the gut-microbiota seems to be a promising treatment of chronic pain.[1,2] In future, gut microbiome analysis might help to screen patients at risk of postoperative cognitive dysfunction, postoperative pain, chronic pain and opioid tolerance and alteration of gut microbiota by use of prebiotics, postbiotics, dietary, and life-style changes might provide therapeutic benefit in such patients. However, this hypothesis is based majorly on animal studies and gut microbiome still needs to be explored in humans. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

MP78-09 THE ASSOCIATION BETWEEN GUT MICROBIOME AND ERECTILE DYSFUNCTION

The occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as neurological score, brain water content, Evans blue extravasation, and neuronal injury. Additionally, we studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR, and flow cytometry. EBI was significantly averted by alterations in GM using antibiotics. The altered GM significantly prevented neutrophil infiltration into the brain among inflammatory cells, and this anti-inflammatory effect was observed immediately following SAH onset. The altered GM also prevented neutrophil extracellular trap formation in the brain and blood, indicating the systemic protective effect. The cause of the protective effect was attributed to a significant decrease in aged neutrophils (CXCR4high CD62Llow) by the altered GM. These protective effects against EBI disappeared when the altered GM was recolonized with normal flora. Our findings demonstrated that EBI following SAH is associated with GM, which regulated neutrophil infiltration.

Psychosocial environments impact normative behavioral development in children, increasing the risk of problem behaviors and psychiatric disorders across the life span. Converging evidence demonstrates that early normative development is affected by the gut microbiome, which itself can be altered by early psychosocial environments. However, much of our understanding of the gut microbiome's role in early development stems from nonhuman animal models and predominately focuses on the first years of life, during peri- and postnatal microbial colonization. As a first step to identify if these findings translate to humans and the extent to which these relationships are maintained after initial microbial colonization, we conducted a metagenomic investigation among a cross-sectional sample of early school-aged children with a range of adverse experiences and caregiver stressors and relationships. Our results indicate that the taxonomic and functional composition of the gut microbiome correlates with behavior during a critical period of child development. Furthermore, our analysis reveals that both socioeconomic risk exposure and child behaviors associate with the relative abundances of specific taxa (e.g., Bacteroides and Bifidobacterium species) as well as functional modules encoded in their genomes (e.g., monoamine metabolism) that have been linked to cognition and health. While we cannot infer causality within this study, these findings suggest that caregivers may moderate the gut microbiome's link to environment and behaviors beyond the first few years of life.IMPORTANCE Childhood is a formative period of behavioral and biological development that can be modified, for better or worse, by the psychosocial environment that is in part determined by caregivers. Not only do our own genes and the external environment influence such developmental trajectories, but the community of microbes living in, on, and around our bodies-the microbiome-plays an important role as well. By surveying the gut microbiomes of a cross-sectional cohort of early school-aged children with a range of psychosocial environments and subclinical mental health symptoms, we demonstrated that caregiving behaviors modified the child gut microbiome's association to socioeconomic risk and behavioral dysregulation.

Background:Despite efforts to increase global immunization, vaccination seroconversion in low and middle income countries (LMICs) is often lower than in high income countries (HICs). The reasons for this disparity are not fully understood. Given the role of the gut microbiome in immune development, we investigated the relationship between the gut microbiome and polio vaccine seroconversion in children in the Democratic Republic of the Congo (DRC).Methods:This cross-sectional analysis included children ages 6-24 months old (n=90) enrolled in the DRC. Vaccine history was obtained from health records and/or self-report and poliovirus serostatus surveyed using dried blood spots. Nutritional status was evaluated using anthropomorphic measures. Microbiome profiling (16S rRNA gene) was performed and associations with poliovirus serostatus and malnutrition were examined.Results:The average age of the study population was 13.6 months (SD=5.6) with 58% female. Poliovirus seropositivity was 65.5% and 22% of the children were malnourished. We found that presence of Campylobacter and Veillonella, especially at an early age, was associated with low poliovirus vaccination seroconversion. These bacterial taxa differed from those associated with malnutrition.Conclusions:The presence of enteropathogens such as Campylobacter at a young age could be an important factor contributing to low vaccination seroconversion in children in LMICs.

Implications of the gut microbiome in cardiovascular diseases: Association of gut microbiome with cardiovascular diseases, therapeutic interventions and multi-omics approach for precision medicine

Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD. We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV. We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis. The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid). This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.