The COVID-Gut Connection
From the beginning, I have maintained that the best defense against COVID-19 is an optimally functioning immune system. Nothing has changed. As more data about the virus accrues, this premise holds true. The fact that so few "big names" in the conventional medical system are encouraging personal immune optimization befuddles me. Nevertheless, as the SARS-CoV-2 global pandemic marches on, I will continue to cite research that promotes the message: Heal your gut, get healthy, and stay healthy.
As the title of this post suggests, there is growing evidence that the gut is involved in COVID-19. This is related to at least three reasons:
The first clue that there is a link between the gut and COVID is the fact that somewhere between 10-50% of patients, depending on which study you read, develop gastrointestinal symptoms including nausea, vomiting, and diarrhea, and some show evidence of intestinal inflammation (1). This is the easiest point to understand. COVID can cause GI symptoms in a lot of people and therefore it involves the gut in some way. Recent studies have shown that, while a respiratory virus, infection with influenza changes the gut microbial constituency (i.e. the microbiome) that then leads to an imbalance (i.e. dysbiosis) that favors inflammation (2,3). Well, it now appears that something similar happens with COVID-19 (4), and this may be the reason for the GI involvement. One study showed that around 20% of people with COVID-19 continue to have virus in their stool even after the respiratory tract tests "virus-free" (5).
The next important link of COVID and the gut is the way in which SARS-CoV-2 infects human cells. The virus attaches to a receptor known as ACE2 which stands for "angiotensin converting enzyme 2." This receptor is not only found in the respiratory tract, but it also is abundant in the cells lining the stomach, small intestine, and large intestine (5,6). SARS-CoV-2 invades the intestinal cells that have ACE-2 which causes inflammation in these tissues. This is yet another way in which the gut is involved in the pathogenesis of COVID-19.
The third connection between SARS-CoV-2 and the gut is where I want to focus most of the attention: The GI microbiome. The gastrointestinal microbiome is the trillions of microbes that inhabit the human gut. Thousands of studies show that the gut microbiome has a profound impact on health and disease. Just a couple of studies are listed in this post (7,8). What it all boils down to is this: There is evidence that dysbiosis may make a person more susceptible to COVID-19 (9,10) AND if a person with an out-of-balance microbiome (dysbiosis) contracts COVID-19, their disease course may be worse (11). This is fascinating research and much more needs to be done, but at this point in the game what conclusions can we make?
In my opinion, this is what everyone should be doing:
Optimize your immune system--particularly relating to the "gut-lung axes". Masks and social distancing may have their place, but these pale in comparison to an optimally functioning immune system. A science-based approach to immune optimization will be the subject of coming articles. Stay tuned!
Optimize the lining of your respiratory and gastrointestinal systems. This is the first line of defense. It needs to be a strong one. More to come on this also.
Optimize your microbiome. Let's get this started by getting on a high quality probiotic. Most studies have focused on what I call "Type 1 Probiotics" which are based on multiple strains of Lactobacillus species/strains as well as Bifidobacterium species/strains. Sure, this is not all that's necessary, but it's a good start. Studies show that these probiotics can help regulate your immune system (12)--an important role when you consider that most of the deaths from COVID-19 stem from "cytokine storm" which is an unregulated, hyper-reactivity of the immune system. I will also be writing articles on the benefits of probiotics in the coming weeks, but I wanted to get this foundational information out there so that we can build on it. In the meantime, if you're not taking a medical-grade probiotic--get on one. If you want my recommendations for the best, give me a call.
Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Effect of Gastrointestinal Symptoms in Patients With COVID-19. Gastroenterology. 2020 Jun;158(8):2294-2297. doi: 10.1053/j.gastro.2020.03.020. Epub 2020 Mar 19. PMID: 32199880; PMCID: PMC7270807.
Bradley KC, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S, Fuchs SY, Staeheli P, Wack A. Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection. Cell Rep. 2019 Jul 2;28(1):245-256.e4. doi: 10.1016/j.celrep.2019.05.105. PMID: 31269444.
Deriu E, Boxx GM, He X, Pan C, Benavidez SD, Cen L, Rozengurt N, Shi W, Cheng G. Influenza Virus Affects Intestinal Microbiota and Secondary Salmonella Infection in the Gut through Type I Interferons. PLoS Pathog. 2016 May 5;12(5):e1005572. doi: 10.1371/journal.ppat.1005572. PMID: 27149619; PMCID: PMC4858270.
Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C, Lu H, Zheng B, Zhang J, Yan R, Zhang H, Jiang H, Xu Q, Guo J, Gong Y, Tang L, Li L. Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza. Clin Infect Dis. 2020 Jun 4:ciaa709. doi: 10.1093/cid/ciaa709. Epub ahead of print. PMID: 32497191; PMCID: PMC7314193.
Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020 May;158(6):1831-1833.e3. doi: 10.1053/j.gastro.2020.02.055. Epub 2020 Mar 3. PMID: 32142773; PMCID: PMC7130181.
Lei HY, Ding YH, Nie K, Dong YM, Xu JH, Yang ML, Liu MQ, Wei L, Nasser MI, Xu LY, Zhu P, Zhao MY. Potential effects of SARS-CoV-2 on the gastrointestinal tract and liver. Biomed Pharmacother. 2021 Jan;133:111064. doi: 10.1016/j.biopha.2020.111064. Epub 2020 Nov 28. PMID: 33378966; PMCID: PMC7700011.
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234. PMID: 22699609; PMCID: PMC3564958.
Belkaid Y, Harrison OJ. Homeostatic Immunity and the Microbiota. Immunity. 2017 Apr 18;46(4):562-576. doi: 10.1016/j.immuni.2017.04.008. PMID: 28423337; PMCID: PMC5604871.
Ferreira C, Viana SD, Reis F. Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update. Microorganisms. 2020 Dec 28;9(1):53. doi: 10.3390/microorganisms9010053. PMID: 33379162; PMCID: PMC7824665.Gut microbiota may underlie the predisposition of healthy individuals to COVID-19
Wanglong Gou, Yuanqing Fu, Liang Yue, Geng-dong Chen, Xue Cai, Menglei Shuai, Fengzhe Xu, Xiao Yi, Hao Chen, Yi Zhu, Mian-li Xiao, Zengliang Jiang, Zelei Miao, Congmei Xiao, Bo Shen, Xiaomai Wu, Haihong Zhao, Wenhua Ling, Jun Wang, Yu-ming Chen, Tiannan Guo, Ju-Sheng Zheng. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. medRxiv 2020.04.22.20076091; doi: https://doi.org/10.1101/2020.04.22.20076091
Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Jan 11:gutjnl-2020-323020. doi: 10.1136/gutjnl-2020-323020. Epub ahead of print. PMID: 33431578; PMCID: PMC7804842.
Zhang CX, Wang HY, Chen TX. Interactions between Intestinal Microflora/Probiotics and the Immune System. Biomed Res Int. 2019 Nov 20;2019:6764919. doi: 10.1155/2019/6764919. PMID: 31828119; PMCID: PMC6886316.