SARS-COV-19: Fiber And Fish Oil Provide Prevention

Part 6: Fermentable fiber and DHA strengthen mitochondria and antiviral immunity

Posted Jul 09, 2020

Dietary fiber and its fermentation products, especially the short-chain fatty acids (SCFAs) acetate, butyrate, and propionate, have numerous beneficial effects. They can ameliorate chronic inflammatory diseases, improve immune responses beyond the gastrointestinal system, such as influencing the lung and brain, dampen immune responses, and act on immune cells, such as regulatory T cells, dendritic cells, neutrophils, macrophages, memory responses of CD8+ T cells, and T helper cell differentiation. SCFAs can influence metabolism in the liver, muscle, immune cells, and adipose tissue(1)

Fermentable fiber studies (i.e., inulin) with humans and mice found that the high fiber diet (HFD) specifically increased colon or gut bacteria with SCFAs that reduced type 2 diabetes symptoms as measured by glucose tolerance tests and hemoglobin AIC.  When the stools from both patient groups were transplanted into germ-free mice, those receiving stool from the HFD patients had the best outcomes. These findings reinforce the importance of the gut microbiota, or all the organisms inhabiting the human digestive tract, as the mediator of health and change(2).

The enzymes in the mouth and upper small intestine, such as amylase and ptyalin, cannot digest prebiotic fibers, such as inulin, which pass relatively unchanged to the large intestine, where they are fermented into SCFAs. Inulin is water-soluble and found in many plants that use it to store energy in their roots instead of starch. Inulin has up to 10 percent of the sweetness of sugar, but only 25-35 percent of the food energy of sugar and starch with many added health benefits noted earlier.  High-performance inulin at 10 grams daily in type 2 diabetic women increased the antioxidant capacity while decreasing body weight and glycemic indices(3). A teaspoon is 4.2 grams, and one twice daily would be essentially 10 grams. There are presently no studies with SARS-CoV or COVID-19 and a diet rich in fermentable fiber. Previous work with influenza regarding antiviral immunity is instructive(1).

Figure 1: (1)

 10.1016/j.immuni.2018.04.022.
Effects of low fiber and high fiber-rich diets.
Source: 1. Trompette, A., Gollwitzer, ES., Pattaroni, C., et al.: Dietary Fiber Confers Protection against Flu by Shaping Ly6c- Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism. Immunity. 2018 May 15;48(5):992-1005.e8. DOI: 10.1016/j.immuni.2018.04.022.

In mice born and raised on a low-fiber diet, a control group supplemented with cellulose (a poorly fermentable diet) was compared to the test group on a high-fiber diet (HFD) supplemented with inulin. Both groups of now-adult mice were exposed intranasally to the influenza A virus (IAV), which uses the same ACE-2 receptor as coronaviruses. HFD mice had prolonged survival and improved clinical scores. They also experienced reduced pulmonary resistance, related to milder airway constriction, increased elasticity, and, therefore, better lung function.

The control mice's lungs had large accumulations of red blood cells in their lung tissue, indicating destruction and vascular leakage. Other measures of immunopathology were decreased in HFD fed mice. 

Additional antiviral immunity effects of HFD with inulin (figure 1) included: 1) alteration of the intestinal microbiota with increasing SCFAs, especially butyrate. Moreover, “supplementing the drinking water with butyrate for two weeks prior to and throughout the infection resulted in protections similar to that elicited by an HFD.” 2) The prevention of excessive neutrophil (white blood cells) influx into the airways by decreasing CXCL1 (a potent neutrophil chemoattractant) produced by lung macrophages and monocytes. 3) Though there were more Ly6c- patrolling monocytes in the blood, bone marrow, and lungs, they were preferentially differentiated into alveolar and interstitial (between cells) macrophages with a less inflammatory “M2” phenotype also called “alternatively activated macrophages” (AAMs). This reduced airway neutrophils and damage. (4)

CD8+ T lymph cell activation occurred with specific anti-influenza viral effect, and a high cytotoxic cell killing capacity was found(1). There are two types of CD8+ T cells. Memory T cells that have been previously exposed to an infectious agent or a foreign body that they know how to fight and “naïve” T cells that have never fought anything. Because we have had no exposure to COV-2 before, the memory T cells are not able to mobilize. The battle is left to the new “naïve” T cell troops. Fortunately, inulin activates these T cells with specific antiviral and high cytotoxic capacity, making them potent viral killing T cells.

Trompette and associates summarized(1):

… our data demonstrate that dietary fiber and SCFAs can protect against severe influenza infection by reducing tissue damage and by boosting adaptive anti-viral immunity. SCFAs have predominantly been associated with immunoregulation and the prevention of exaggerated inflammation;  however, our work highlights a dual role of SCFAs. By tuning down excessive innate responses, promoting tissue-protective mechanisms, and stimulating specific adaptive immunity, dietary fiber and SCFAs can create an immune balance that ultimately protects against disease.

The importance of the microbiota in another study(4) is again revealed in their modulation and fine-tuning of interferon, which protects lung tissue in mice (all mammals) from viral infections. If the mice were given antibiotics which killed or disrupted the microbiota, their lung tissue was more easily infected by influenza. If the antibiotic-exposed mice were given fecal material of control mice orally by a tube to their stomach (fecal transplant), they became more resistant. That is, it increased the production of interferon proteins with various antiviral functions and fine-tuned interferon viral resistance.  (Figure 2). 

Figure 2:(4) 

 10.1016/j.celrep
The effects of antibiotics and fecal transplant in mice on influenza infection, interferon, and its receptors and genes.
Source: 4. Bradley, K. C., Finsterbusch, K., Schnepf, D., et al.: Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection. Cell Rep.2019.05.105orts. 2 July 2019, 28(1), 245-256. DOI: 10.1016/j.celrep

Omega 3 fatty acids are part of the cellular membrane of all human tissues, including muscle and mitochondria. Fish oil omega 3s (FOO3s) from supplementation are incorporated into our cellular membranes(5). They can lower the mortality rate for people with cardiovascular disease (CVD).

FOO3s can also regulate blood vessel lining cells (endothelial) by decreasing oxidative stress, atherosclerotic plaque formation, and inflammation. Even in mice fed a high-fat lard diet, FOO3s supplementation resulted in a 54 percent decrease in plaque formation. It also increased nitrous oxide (NOS) release and endothelial NO synthase activity necessary for vascular health and sexual function. Additionally, it lowered the levels of mitochondrial oxidative stress and cytochrome C release, reflecting improved mitochondrial health(6).

FOO3s can interact favorably with fermentable fiber, which produces butyrate (e.g., pectin in apples) to increase mitochondrial energy production and the death of mouse colon cancer cells(5). When mitochondria are compromised by a viral infection, they are no longer key (8) to regulating the apoptotic (cellular death) pathway whereby damaged cells are selectively eliminated (autophagy) that can contribute to cancer formation. FOO3s are a mixture of two polyunsaturated fatty acids, EPA, and DHA, which together have been shown to decrease inflammatory states and modulate immune mechanisms, including B cell activity. B cells are involved in antibody production and cytokine (regulate immunity and inflammation) secretion(9), which is enhanced in lean and obesemice by FOO3s(10).

There is evidence in rodent studies that DHA is more effective than EPA(10). Newly diagnosed diabetics have a decreased production of B cell cytokines, and obese humans and mice (two of the risk factors for COVID-19) have a lower antibody response to influenza infection (utilizes the same ACE-2 receptor) or vaccination. In these same mice, DHA improved “influenza-specific antibody production”(10). In a human pilot study, the high DHA fish oil supplement (0.5g EPA and 2.0 g DHA daily) increased isolated B cell cytokine secretion relative to baseline, while olive oil and regular fish oil concentrate did not. However, more research is needed to clarify a specific benefit(10) and FOO3s beneficial interaction with fermentable fiber. How we can help our mental health and public policy is next in Part 7.

This is not meant to be medical advice. The reader needs to consult their health care provider before making any medical decisions.

References

1. Trompette, A., Gollwitzer, ES., Pattaroni, C., et al: Dietary Fiber Confers Protection against Flu by Shaping Ly6c- Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism. Immunity. 2018 May 15;48(5):992-1005.e8. doi: 10.1016/j.immuni.2018.04.022.

2. Zhao, L., Zhang, F., Ding, X., et al: Gut Bacteria Selectively Promoted by Dietary Fibers Alleviate Type 2 Diabetes. Science 2018,359, 1151-1156.

3. Ryback, R.: Why French women don’t get fat? Unpublished manuscript.

4. Bradley, K. C., Finsterbusch, K., Schnepf, D., et al: Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection. Cell Reports. 2 July 2019, 28(1), 245-256.  doi.org/10.1016/j.celrep.2019.05.105

5. Gerling, C. J., Mukai, K., Chabowski, A., et al.: Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation. Front Physiol. 2019; 10: 348. 2019 Mar 29. doi: 10.3389/fphys.2019.00348

6. Sun, R., Wang, X., Xia, M. Dietary Supplementation With Fish Oil Alters the Expression Levels of Proteins Governing Mitochondrial Dynamics and Prevents High-Fat Diet-Induced Endothelial Dysfunction. Br J Nutr. 2014 Jul 28;112(2):145-53. doi: 10.1017/S0007114514000701.

7. Fan, Y. Y., Vaz, F. M., Chapkin, R. S. Dietary Fat and Fiber Interactively Modulate Apoptosis and Mitochondrial Bioenergetic Profiles in Mouse Colon in a Site-Specific Manner. Eur J Cancer Prev. 2017 Jul;26(4):301-308. doi: 10.1097/CEJ.0000000000000263.

8. Baixauli, F., Acín-Pérez, R., Villarroya-Beltrí, C., et al.: Mitochondrial Respiration Controls Lysosomal Function During Inflammatory T Cell Responses. Cell Metab. 2015 Sep 1;22(3):485-98. doi: 10.1016/j.cmet.2015.07.020.

9. Waffarn, E. E., Baumgarth, N. Protective B cell responses to flu – no fluke! J Immunol. 2011 Apr 1; 186(7):3823–3829. doi: 10.4049/jimmunol.1002090

10. Guesdon, W., Kosaraju, R., Brophy, P., et al.: Effects of fish oils on ex vivo B-cell responses of obese subjects upon BCR/TLR stimulation: a pilot study. J. Nurt. Biochem. 2017, Nov 2, 53, 72-80. doi.org/10.1016/j.jnutbio.2017.10.009