The gut–brain axis and pain signalling mechanisms in the gastrointestinal tract
Related Articles
Modulating neuroplasticity for chronic pain relief: noninvasive neuromodulation as a promising approach
Chronic neuropathic pain is a debilitating neuroplastic disorder that notably impacts the quality of life of millions of people worldwide. This complex condition, encompassing various manifestations, such as sciatica, diabetic neuropathy and postherpetic neuralgia, arises from nerve damage or malfunctions in pain processing pathways and involves various biological, physiological and psychological processes. Maladaptive neuroplasticity, known as central sensitization, plays a critical role in the persistence of chronic neuropathic pain. Current treatments for neuropathic pain include pharmacological interventions (for example, antidepressants and anticonvulsants), invasive procedures (for example, deep brain stimulation) and physical therapies. However, these approaches often have limitations and potential side effects. In light of these challenges, interest in noninvasive neuromodulation techniques as alternatives or complementary treatments for neuropathic pain is increasing. These methods aim to induce analgesia while reversing maladaptive plastic changes, offering potential advantages over conventional pharmacological practices and invasive methods. Recent technological advancements have spurred the exploration of noninvasive neuromodulation therapies, such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation and transcranial ultrasound stimulation, as well as innovative transformations of invasive techniques into noninvasive methods at both the preclinical and clinical levels. Here this review aims to critically examine the mechanisms of maladaptive neuroplasticity in chronic neuropathic pain and evaluate the efficacy of noninvasive neuromodulation techniques in pain relief. By focusing on optimizing these techniques, we can better assess their short-term and long-term effects, refine treatment variables and ultimately improve the quality of neuropathic pain management.
Crosstalk between gut microbiotas and fatty acid metabolism in colorectal cancer
Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.
Microbiome-based interventions to modulate gut ecology and the immune system
The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.
Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability
Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host’s metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.
Bifidobacterium animalis subsp. lactis A6 ameliorates bone and muscle loss via modulating gut microbiota composition and enhancing butyrate production
Systematic bone and muscle loss is a complex metabolic disease, which is frequently linked to gut dysfunction, yet its etiology and treatment remain elusive. While probiotics show promise in managing diseases through microbiome modulation, their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated. Employing dextran sulfate sodium (DSS)-induced gut dysfunction model and wide-spectrum antibiotics (ABX)-treated mice model, our study revealed that gut dysfunction instigates muscle and bone loss, accompanied by microbial imbalances. Importantly, Bifidobacterium animalis subsp. lactis A6 (B. lactis A6) administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria. This intervention effectively restored depleted butyrate levels in serum, muscle, and bone tissues caused by gut dysfunction. Furthermore, butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria. Importantly, butyrate inhibited the NF-κB pathway activation, and reduced the secretion of corresponding inflammatory factors in T cells. Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B. lactis A6. These discoveries offer new microbiome directions for translational and clinical research, providing promising strategies for preventing and managing musculoskeletal diseases.
Responses