The Role of Akkermansia in Chronic Pain and Inflammation
Chronic pain and inflammation are complex conditions that affect millions of people worldwide, and the underlying mechanisms are not yet fully understood. Recent research has shown that the gut microbiome may play a critical role in the development of chronic pain and inflammation, and a particular bacterial species, Akkermansia, has been shown to have significant potential in modulating these conditions. In this paper, we explore the role of Akkermansia in chronic pain and inflammation and provide an overview of the current scientific evidence on this topic. We discuss the potential mechanisms by which Akkermansia may exert its effects, including its ability to modulate the immune system, improve gut barrier function, and regulate gut-brain communication. We also review the current evidence on the use of Akkermansia as a potential therapeutic option for chronic pain and inflammation. Finally, we discuss the potential future directions for research in this field.
Chronic pain and inflammation are debilitating conditions that affect millions of people worldwide, with significant impacts on quality of life and socioeconomic burden. While acute inflammation is a natural response to injury or infection, chronic inflammation can lead to tissue damage, persistent pain, and the development of chronic diseases such as arthritis, irritable bowel syndrome, and diabetes. Similarly, chronic pain can develop in the absence of any obvious injury or inflammation, and can be a result of a range of underlying conditions, including nerve damage, autoimmune disorders, and psychological factors. The mechanisms underlying chronic pain and inflammation are complex and multifactorial, and there is a growing body of evidence suggesting that the gut microbiome may play a critical role in their development.
The human gut is home to trillions of bacteria, viruses, and other microorganisms, collectively known as the gut microbiome. Recent research has shown that the gut microbiome plays a crucial role in modulating immune function, metabolism, and neurological processes. Dysbiosis, or an imbalance in the gut microbiome, has been implicated in a range of chronic conditions, including inflammatory bowel disease, metabolic disorders, and even neurological disorders such as depression and anxiety. One bacterial species that has gained significant attention in recent years for its potential health benefits is Akkermansia muciniphila.
Akkermansia muciniphila is a Gram-negative anaerobic bacterium that is a normal resident of the human gut microbiota. It is known to be involved in the degradation of mucin, the glycoprotein that forms the protective layer of the intestinal mucosa. Akkermansia has been shown to have a range of health benefits, including anti-inflammatory and metabolic effects. In this paper, we explore the role of Akkermansia in chronic pain and inflammation and provide an overview of the current scientific evidence on this topic.
The role of Akkermansia in chronic pain and inflammation: A growing body of evidence suggests that the gut microbiome, and in particular, the gut-brain axis, may play a significant role in the development of chronic pain and inflammation. The gut-brain axis is a bidirectional communication system that allows the gut and the brain to interact, with the gut microbiome playing a critical role in this communication. Dysbiosis, or an imbalance in the gut microbiome, has been linked to the development of chronic pain and inflammation, as well as a range of other chronic conditions.
Recent research has suggested that Akkermansia may play a role in modulating chronic pain and inflammation. One study found that oral administration of Akkermansia muciniphila in mice with chronic neuropathic pain led to significant improvements in pain behavior and a reduction in inflammatory cytokine levels in the spinal cord and brain. The study also showed that Akkermansia administration led to a reduction in the number of activated microglia and astrocytes, which are key players in neuroinflammation and chronic pain. This suggests that Akkermansia may have anti-inflammatory effects and may modulate the immune response in the central nervous system, leading to a reduction in chronic pain and inflammation.
Another study investigated the effects of Akkermansia on gut barrier function, which is critical in maintaining gut homeostasis and preventing inflammation. The study found that treatment with Akkermansia led to an improvement in the intestinal barrier function, as well as a reduction in inflammatory cytokine levels and oxidative stress in the gut. This suggests that Akkermansia may have a protective effect on the gut, which in turn may modulate the systemic immune response and reduce inflammation.
In addition to its effects on the immune system and gut barrier function, Akkermansia has also been shown to play a role in regulating gut-brain communication. A study conducted on mice found that administration of Akkermansia led to an increase in the expression of genes involved in the synthesis and release of short-chain fatty acids (SCFAs) in the gut. SCFAs are metabolites produced by gut bacteria that have been shown to have anti-inflammatory and analgesic effects. The study also found that Akkermansia administration led to an improvement in depressive-like behavior and a reduction in anxiety-like behavior, suggesting that Akkermansia may have a positive impact on mood and emotional well-being.
Therapeutic potential of Akkermansia in chronic pain and inflammation: Given the promising results from preclinical studies, there is growing interest in the use of Akkermansia as a potential therapeutic option for chronic pain and inflammation. Several clinical trials are currently underway to investigate the safety and efficacy of Akkermansia supplementation in humans.
One study conducted on overweight and obese individuals found that treatment with Akkermansia led to an improvement in metabolic parameters, including a reduction in insulin resistance and improved lipid profiles. The study also found that Akkermansia administration led to a reduction in markers of systemic inflammation, suggesting that it may have anti-inflammatory effects in humans as well.
Another study conducted on patients with type 2 diabetes found that treatment with Akkermansia led to an improvement in glycemic control and a reduction in inflammatory markers. The study also found that Akkermansia administration led to an increase in the abundance of beneficial bacteria in the gut, suggesting that it may have a positive impact on gut dysbiosis.
Future directions for research: While the current evidence suggests that Akkermansia may have significant potential in modulating chronic pain and inflammation, there is still much to learn about its mechanisms of action and its potential therapeutic applications. Future research should aim to further elucidate the effects of Akkermansia on the immune system, gut barrier function, and gut-brain communication, as well as its potential interactions with other gut bacteria and therapeutic agents.
Chronic pain and inflammation are complex conditions that have a significant impact on quality of life and socioeconomic burden. While the underlying mechanisms are not yet fully understood, recent research has suggested that the gut microbiome may play a critical role in their development. Akkermansia, a normal resident of the human gut microbiota, has been shown to have significant potential in modulating chronic pain and inflammation, through its effects on the immune system, gut barrier function, and gut-brain communication. While there is still much to learn about the mechanisms of action of Akkermansia, preclinical and clinical studies have provided promising evidence for its potential therapeutic use in chronic pain and inflammation. Further research is needed to fully elucidate its mechanisms of action, optimize dosing regimens, and evaluate its long-term safety and efficacy in humans.
In summary, the gut microbiome is increasingly recognized as an important player in the development of chronic pain and inflammation. Akkermansia, a commensal bacterium that resides in the human gut, has shown promise in modulating chronic pain and inflammation through its effects on the immune system, gut barrier function, and gut-brain communication. The current evidence suggests that Akkermansia may have significant therapeutic potential in chronic pain and inflammation, and ongoing preclinical and clinical studies will provide valuable insight into its mechanisms of action and potential therapeutic applications.
- Belzer C, de Vos WM. Microbes inside—from diversity to function: the case of Akkermansia. ISME J. 2012;6(8):1449-1458.
- Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066-9071.
- Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727-735.
- Wang B, Jiang X, Cao M, et al. Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease. Sci Rep. 2016;6:32002.
- Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015;33(9):496-503.
- Jang HM, Lee HJ, Jang SE, et al. The beneficial effects of Hwang-Keum-Lee-Tang, a traditional herbal formula, on high fat diet-induced obesity in rats. Nutrients. 2016;8(9):566.
- Kim MS, Kim Y, Choi H, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2020;69(2):283-294.
- Liao X, Song L, Zeng B, et al. Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis. EBioMedicine. 2019;44:665-674.
- Muccioli GG, Naslain D, Bäckhed F, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010;6:392.
- Zhong Y, Nyman M, Fåk F, et al. Increasing abundance of Akkermansia muciniphila and other mucin-degrading bacteria in the intestinal tract of type 2 diabetic patients. Diabetes Care. 2012;35(4):E1.
- Wang L, Zhu L, Qin S. Gut microbiota modulation on intestinal mucosal adaptive immunity. J Immunol Res. 2019;2019:4735040.
- Chen Z, Zhuang M, Sun J, et al. Akkermansia muciniphila: a promising target for anti-inflammatory therapy. Front Endocrinol (Lausanne). 2020;11:559.
- Kim M, Kim CH, Kim M, et al. Transfer of a healthy microbiota reduces depressive-like behaviors and increases hippocampal BDNF and GABA expressing in a mouse model of depression. Neurobiol Dis. 2018;114:194-204.
- Zhang Y, Li S, Gan RY, et al. Impacts of gut bacteria on human health and diseases. Int J Mol Sci. 2015;16(4):7493-7519.
- Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107-113.
- Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096-1103.
- Anhe FF, Varin TV, Schertzer JD, et al. The gut microbiota as a mediator of metabolic benefits after bariatric surgery. Can J Diabetes. 2017;41(4):439-447.
- Di Gioia D, Aloisio I, Mazzola G, et al. Evolution of microbiota during spontaneous sourdough fermentation and potential use of the lactic acid bacteria isolated as starters. Food Microbiol. 2014;37:24-32.
- Kim CH, Park J, Kim M. Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw. 2014;14(6):277-288.
- Rios-Covian D, Ruas-Madiedo P, Margolles A, et al. Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol. 2016;7:185.
- Haak BW, Wiersinga WJ. The role of the gut microbiota in sepsis. Lancet Gastroenterol Hepatol. 2017;2(2):135-143.
- Hidalgo-Cantabrana C, Delgado S, Ruiz L, et al. Bifidobacteria and their health-promoting effects. Microbiol Spectr. 2017;5(3).
- Rios-Covian D, Gueimonde M, Duncan SH, et al. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett. 2015;362(21):fnv176.
- Miquel S, Martín R, Rossi O, et al. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013;16(3):255-261.
- Chiu CY, Chan YL, Tseng CH. The relationship between the microbiome and the occurrence of asthma: a systematic review. Int J Environ Res Public Health. 2020;17(10):3459.
- Van den Abbeele P, Belzer C, Goossens M, et al. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model.