Andrographis, cat’s claw, humic acid, and monolaurin
In 2020 we became all too aware of how infectious disease seriously threatens the health of people worldwide. Fortunately, there is ongoing investigation of nutrients, herbs, and other natural substances that may help fight common injurious microbes, especially when conventional medicine fails to deliver. In today’s post we’ll discuss four natural substances that may provide infection-fighting benefits: andrographis, cat’s claw, humic acid, and monolaurin.
Also known as King of Bitters, Indian Echinacea, and Kalmegh, andrographis (Andrographis paniculata) is a bitter-tasting herb that has long been used in traditional medicine for the treatment of infections and other maladies.,
The main active ingredient, known as andrographolide,, has been shown to reduce the infectivity of numerous human viruses, including influenza.,,, The influenza virus enters (and thus infects) our cells by way of the surface protein hemagglutinin. Research suggests that andrographolide may interfere with hemagglutinin and block its binding to cellular receptors, thus protecting us from infection. In this respect, the action of andrographolide may be similar to that of certain established influenza drugs and antibody therapies.
The effects of andrographolide, however, extend beyond its direct antiviral activity. It is among a handful of plant substances that can induce the expression of human β-defensin-3 (HBD3), one of the most efficient antimicrobial peptides in the body. Defensins such as HBD3 play a crucial role in innate immunity. Andrographolide also increases the expression of Nrf2, a master regulator of the antioxidant response.,, The activation of Nrf2 helps limit oxidative damage during infections, and may help limit viral replication, as shown for the hepatitis C virus.
A reduction in lung inflammation and pathology is an important feature of andrographolide’s mechanism of action.
In a mouse model of influenza, andrographolide treatment was shown to diminish lung pathology, decrease viral loads, and increase survival rate. A reduction in lung inflammation and pathology is an important feature of andrographolide’s mechanism of action., Virus-associated lung inflammation, which occurs when the immune system floods the body with cytokines, can lead to respiratory failure.
A meta-analysis of 33 randomized controlled trials found that andrographis also may help ameliorate the symptoms of acute respiratory tract infections in adults and children. Andrographolide relieves inflammation by inhibiting a key pathway involving NF-κB, which controls the expression of a wide range of pro‐inflammatory signals and contributes to viral pathology.,, Andrographolide also reduces levels of interleukin (IL)-6, a pro-inflammatory cytokine that is a target for the treatment of severe respiratory infections. Because it suppresses these pathways, andrographolide may help support lung function during respiratory infections.
Cat’s claw (Uncaria tomentosa), an herb that grows wild in the Peruvian highlands, has long been used by indigenous tribes in the Amazonian region to treat inflammatory conditions, including arthritis, allergies, and asthma., U. tomentosa contains more than 30 bioactive compounds, including mitraphylline, an alkaloid that has been shown to modulate the body’s immune responses.,,
Cat’s claw has been shown to increase the ability of white blood cells to ingest and subsequently destroy invaders.
Cat’s claw is one of the few Amazonian herbs shown to increase phagocytic activity, the ability of human white blood cells to ingest and subsequently destroy invaders. Specific studies of U. tomentosa extracts revealed an antibacterial effect against Pseudomonas aeruginosa and Staphylococcus aureus, which are opportunistic pathogens. Infections with respiratory viruses are known to enable secondary infections with pneumonia-causing bacteria like these; cat’s claw may protect against this.,
U. tomentosa extracts have been shown to block the infection of human cells by some viruses, including Dengue virus, the most common mosquito-borne viral infection in the world., However, cat’s claw is best known for its anti-inflammatory properties. It modulates inflammation by suppressing levels of NF-κB and tumor necrosis factor (TNF)-α, a master regulator of inflammatory processes.,, Its pronounced effect on TNF-α may provide a clue as to the utility of cat’s claw in various clinical conditions. For example, anti-TNF antibodies have been used to treat inflammatory conditions such as rheumatoid arthritis (RA), and studies have shown that cat’s claw may ameliorate the symptoms of RA in a similar manner.
When it comes to respiratory infections, the production of TNF is part of the body’s attempt to clear infections. When TNF spirals out of control, however, lung damage can ensue.,, It’s not surprising, then, that therapies that suppress TNF are under investigation for the treatment of severe respiratory infections. Because cat’s claw not only inhibits TNF, but also ameliorates lung inflammation in mice,,, it is a promising candidate for human clinical investigations.
Named after humus, the organic component of soil, humic substances arise from the decomposition of animal and plant residues in water, peat, soil, and sediment. Humic substances can be fractionated into humin, humic acid (HA), and fulvic acid.,
HA has a plethora of functional groups with binding properties, making it capable of binding a broad spectrum of viruses.,,,, Studies of lakes that contain high amounts of HA suggest that viral numbers are lowered by the presence of these substances.
The antiviral effect of humic acid is directed specifically against an early stage of infection – the one in which the virus attaches to our cells.
In mammalian cells, the antiviral effect of HA is directed specifically against an early stage of infection – the one in which the virus attaches to our cells.,,,, HA and its synthetic analogues were shown to reduce the infectivity of herpes simplex virus (HSV),,, hepatitis B virus (HBV), human immunodeficiency virus (HIV),,,, and Coxsackie virus,, all of which afflict humans. In a study of HBV, researchers found that HA not only inhibited viral replication, but also caused infected cells to die off, without harming the healthy, uninfected cells.
A component of HA, protocatechuic acid (PCA), has been shown to inhibit the replication of influenza viruses in the laboratory and in animals. In a study of influenza in mice, fewer than 60% of the control animals survived the infection, while nearly all of the animals who were given PCA survived.
Owing to its antimicrobial properties, HA has been used as a feed additive to improve poultry performance and health. In both animals and humans, HA has health-promoting effects on the gut and immune system.,, Clinical studies in healthy volunteers showed that supplementation with HA increased the concentration of the colonic microbiota by 20% to 30% without altering its diversity, suggesting that it enhanced the growth of existing healthy bacteria. As an added benefit, HA strongly binds organic pollutants and toxic heavy metals.,,,, HA may thus play a role in reducing heavy metal concentrations and environment-caused illnesses.
Monolaurin, a monoglyceride comprising glycerol and lauric acid (C12), occurs naturally in human milk. In fact, monolaurin is thought to be one of the reasons why breast feeding is so healthful for infants.,,
Monolaurin was first discovered to have antiviral activity over 40 years ago. Since then, numerous laboratory studies have shown that it can suppress the growth and virulence of enveloped viruses, bacteria, and some fungi, including Candida spp.,,, Monolaurin has been shown to have 200 to 400 times more antibacterial activity than lauric acid, a fatty acid found in coconut oil.,,,
Human milk contains approximately 3,000 mcg of monolaurin per ml, compared to 150 mcg per ml in bovine milk, and none in infant formula. The monolaurin in breast milk is thought to suppress the growth of gut pathogens and to encourage the growth of beneficial bacteria, such as lactobacilli. In fact, monolaurin appears to act in a manner similar to that of reutericyclin, a natural antibiotic substance produced by lactobacilli.,
Monolaurin has been shown to reduce the infectivity of 14 different enveloped viruses by more than 99.9% in vitro.
As mentioned, monolaurin inhibits “enveloped” viruses, including influenza. Enveloped viruses are those with an outer wrapping or envelope, which comes from the infected cell in a process called “budding off.” The envelope may play a role in helping a virus survive and infect other cells, and monolaurin may counteract this process by helping to disintegrate the envelope., Monolaurin has been shown to reduce the infectivity of 14 different enveloped viruses by more than 99.9% in vitro.
The membrane-destabilizing activity of monolaurin also inhibits bacterial cell growth (bacteriostatic action) and induces bacterial cell death (bactericidal action). Monolaurin has been shown to inhibit the bacteria associated with pneumonia, including Streptococcus pneumoniae (pneumococcus) and Staphylococcus aureus.,, These bacteria often complicate viral respiratory infections and are associated with more severe disease outcomes.
Last but not least, its beneficial effects on the gut microbiota contribute to monolaurin’s supportive properties. Respiratory viruses can contribute to an imbalanced microbiota and the ensuing diarrhea, and some viruses can even spread to the gastrointestinal tract after a respiratory infection.,, A healthy microbiota can suppress viral infections, while a microbiota that is dysbiotic (out of balance) can make it easier for viruses to take hold.
Andrographis, cat’s claw, humic acid, and monolaurin act via distinct mechanisms to reduce viral infectivity, modulate immunity, and/or reduce the inflammation associated with viral infections. Importantly, unlike drugs that have a single mechanism of action, each of these natural substances attacks the problem in a multifaceted way. The evidence to date is compelling, and justifies further clinical investigations of these natural products.Click here to see References
 Arora R, et al. Potential of complementary and alternative medicine in preventive management of novel H1N1 flu (swine flu) pandemic: thwarting potential disasters in the bud. Evid Based Complement Alternat Med. 2011;2011:586506.
 Perry LM, Metzger J. Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses. Cambridge, Massachusetts: MIT Press; 1980.
 Okhuarobo A, et al. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis. 2014 Jun; 4(3):213–22.
 Gupta S, et al. Broad-spectrum antiviral properties of andrographolide. Arch Virol. 2017 Mar;162(3):611-23.
 Mussard E, et al. Andrographolide, a natural antioxidant: an update. Antioxidants (Basel). 2019 Nov 20;8(12):571.
 Chen JX, et al. Activity of andrographolide and its derivatives against influenza virus in vivo and in vitro. Biol Pharm Bull. 2009 Aug;32(8):1385-91.
 Chen H, et al. Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents. Bioorg Med Chem Lett. 2014 May 15;24(10):2353-9.
 Lee JC, et al. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells. Br J Pharmacol. 2014 Jan;171(1):237-52.
 Seubsasana S, et al. A potential andrographolide analogue against the replication of herpes simplex virus type 1 in vero cells. Med Chem. 2011 May;7(3):237-44.
 Raja J, et al. In silico analysis to compare the effectiveness of assorted drugs prescribed for swine flu in diverse medicine systems. Indian J Pharm Sci. 2014 Jan;76(1):10-8.
 Sechet E, et al. Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3. Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9869–78.
 Park MS, et al. Towards the application of human defensins as antivirals. Biomol Ther (Seoul). 2018 May 1;26(3):242-54.
 Wong DPW, et al. Regulation of the Nrf2 transcription factor by andrographolide and organic extracts from plant endophytes. PLoS One. 2018 Oct 1;13(10):e0204853.
 Ding Y, et al. Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway. Microbes Infect. 2017 Dec;19(12):605-15.
 Gao F, et al. Andrographolide sulfonate attenuates acute lung injury by reducing expression of myeloperoxidase and neutrophil-derived proteases in mice. Front Physiol. 2018 Aug 17;9:939.
 Tan WS, et al. Cigarette smoke-induced lung disease predisposes to more severe infection with nontypeable Haemophilus influenzae: protective effects of andrographolide. J Nat Prod. 2016 May 27;79(5):1308-15.
 Hu XY, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis. PLoS One. 2017 Aug 4;12(8):e0181780.
 Xia YF, et al. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol. 2004 Sep 15;173(6):4207-17.
 Kumar N, et al. NF-kappaB signaling differentially regulates influenza virus RNA synthesis. J Virol. 2008 Oct;82(20):9880-9.
 Kou W, et al. Andrographolide suppresses IL-6/Stat3 signaling in peripheral blood mononuclear cells from patients with chronic rhinosinusitis with nasal polyps. Inflammation. 2014 Oct;37(5):1738-43.
 Betakova T, et al. Cytokines induced during influenza virus infection. Curr Pharm Des. 2017;23(18):2616-22.
 Williams JE. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Uña de Gato and Sangre de Grado. Altern Med Rev. 2001 Dec 1;6(6):567-80.
 Azevedo BC, et al. Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma. J Ethnopharmacol. 2018 May 23;218:76-89.
 Navarro Hoyos M, et al. Phenolic assessment of Uncaria tomentosa L. (cat’s claw): leaves, stem, bark and wood extracts. Molecules. 2015 Dec 18;20(12):22703-17.
 Serrano A, et al. Bioactive compounds and extracts from traditional herbs and their potential anti-inflammatory health effects. Medicines (Basel). 2018 Jul 16;5(3):76.
 Rojas-Duran R, et al. Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa bark. J Ethnopharmacol. 2012 Oct 11;143(3):801-4.
 Montserrat-de la Paz S, et al. Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: skew toward M2 macrophages. J Ethnopharmacol. 2015 Jul 21;170:128-35.
 Della Valle V. Uncaria tomentosa. G Ital Dermatol Venereol. 2017 Dec;152(6):651-7.
 Navarro-Hoyos M, et al. Proanthocyanidin characterization and bioactivity of extracts from different parts of Uncaria tomentosa L. (Cat’s Claw). Antioxidants (Basel). 2017 Feb 4;6(1):12.
 Seki M, et al. Acute infection with influenza virus enhances susceptibility to fatal pneumonia following Streptococcus pneumoniae infection in mice with chronic pulmonary colonization with Pseudomonas aeruginosa. Clin Exp Immunol. 2004 Jul;137(1):35-40.
 Robinson KM, et al. The immunology of influenza virus-associated bacterial pneumonia. Curr Opin Immunol. 2015 Jun;34:59-67.
 Reis SR, et al. Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2. Int Immunopharmacol. 2008 Mar;8(3):468-76.
 Lima-Junior RS, et al. Uncaria tomentosa alkaloidal fraction reduces paracellular permeability, IL-8 and NS1 production on human microvascular endothelial cells infected with dengue virus. Nat Prod Commun. 2013 Nov;8(11):1547-50.
 Sandoval -Chacón M, et al. Antiinflammatory actions of cat’s claw: the role of NF-kappaB. Aliment Pharmacol Ther. 1998 Dec;12(12):1279-89.
 Allen-Hall L, et al. Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB. J Ethnopharmacol. 2010 Feb 17;127(3):685-93.
 Domingues A, et al. Uncaria tomentosa aqueous-ethanol extract triggers an immunomodulation toward a Th2 cytokine profile. Phytother Res. 2011 Aug;25(8):1229-35.
 Mur E, et al. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002 Apr;29(4):678-81.
 Aguilera ER, Lenz LL. Inflammation as a modulator of host susceptibility to pulmonary influenza, pneumococcal, and co-infections. Front Immunol. 2020 Feb 11;11:105.
 La Gruta NL, et al. A question of self-preservation: immunopathology in influenza virus infection. Immunol Cell Biol. 2007 Feb-Mar;85(2):85-92.
 Vareille M, et al. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev. 2011 Jan;24(1):210-29.
 Hussell T, et al. Inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopathology. Eur J Immunol. 2001 Sep;31(9):2566-73.
 de Melo BA, et al. Humic acids: structural properties and multiple functionalities for novel technological developments. Mater Sci Eng C Mater Biol Appl. 2016 May;62:967-74.
 MacCarthy P, et al. Separation of humic substances by pH gradient desorption from a hydrophobic resin. Anal Chem. 1979;51(12):2041-3.
 Mirza MA. Future of humic substances as pharmaceutical excipient. Pharma Sci Analytical Res J. 2018;1(1):180004.
 Perdue EM. Chemical composition, structure, and metal binding properties. In: Hessen DO, Tranvik LJ, eds. Aquatic Humic Substances: Ecology and Biogeochemistry. Berlin, Germany: Springer-Verlag; 1998: 41-61.
 Lu FJ, et al. In vitro anti-influenza virus activity of synthetic humate analogues derived from protocatechuic acid. Arch Virol. 2002;147(2):273-84.
 Helbig B, et al. Anti-herpes simplex virus type 1 activity of humic acid-like polymers and their o-diphenolic starting compounds. Antivir Chem Chemother. 1997 Jun;8(3):265-73.
 Schneider J, et al. Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: mechanism of inhibition. Virology. 1996 Apr 15;218(2):389-95.
 van Rensburg CE, et al. Investigation of the anti-HIV properties of oxihumate. Chemotherapy. 2002 Jul;48(3):138-43.
 Zhernov YV, et al. Supramolecular combinations of humic polyanions as potent microbicides with polymodal anti-HIV-activities. New J Chem. 2017;41(1):212-24.
 Ram AS, et al. High lytic infection rates but low abundances of prokaryote viruses in a humic lake (Vassivière, Massif Central, France). Appl Environ Microbiol. 2011 Aug 15;77(16):5610-8.
 Klöcking R, et al. Anti-HSV-1 activity of synthetic humic acid-like polymers derived from p-diphenolic starting compounds. Antivir Chem Chemother. 2002 Jul;13(4):241-9.
 Meerbach A, et al. In vitro activity of polyhydroxycarboxylates against herpesviruses and HIV. Antivir Chem Chemother. 2001 Nov;12(6):337-45.
 Pant K, et al. Humic acid inhibits HBV-induced autophagosome formation and induces apoptosis in HBV-transfected Hep G2 cells. Sci Rep. 2016 Oct 6;6:34496.
 Klöcking R, Sprössig M. Antiviral properties of humic acids. Experientia. 1972 May 1;28(5):607-8.
 Jacob KK, et al. Humic substances as a potent biomaterials for therapeutic and drug delivery system – a review. Int J App Pharm. 2019;11(3):1.
 Tsutsuki K, Kuwatsuka S. Chemical studies on soil humic acids: degradation of humic acids with potassium hydroxide. Soil Sci. Plant Nutr. 1979 Jun 1;25(2):183-95.
 Ou C, et al. Protocatechuic acid, a novel active substance against avian influenza virus H9N2 infection. PLoS One. 2014 Oct 22;9(10):e111004.
 Arif M, et al. Humic acid as a feed additive in poultry diets: a review. Iran J Vet Res. 2019 Summer;20(3):167-72.
 Swidsinksi A, et al. Impact of humic acids on the colonic microbiome in healthy volunteers. World J Gastroenterol. 2017 Feb 7;23(5):885-90.
 Vetvicka V, et al. The relative abundance of oxygen alkyl-related groups in aliphatic domains is involved in the main pharmacological-pleiotropic effects of humic acids. J Med Food. 2013 Jul;16(7):625-32.
 Vucskits AV, et al. Effect of fulvic and humic acids on performance, immune response and thyroid function in rats. J Anim Physiol Anim Nutr (Berl). 2010 Dec;94(6):721-8.
 Chianese S, et al. Sorption of organic pollutants by humic acids: a review. Molecules. 2020 Feb 19;25(4):918.
 Glynn AW. Fulvic and humic acids decrease the absorption of cadmium in the rat intestine. Arch Toxicol. 1995;70(1):28-33.
 Vetvicka V, et al. Humic acid and glucan: protection against liver injury induced by carbon tetrachloride. J Med Food. 2015 May;18(5):572-7.
 Krempaská K, et al. Humic acids as therapeutic compounds in lead intoxication. Curr Clin Pharmacol. 2016;11(3):159-67.
 Uhle ME, et al. Binding of polychlorinated biphenyls to aquatic humic substances: the role of substrate and sorbate properties on partitioning. Environ Sci Technol. 1999 Aug 15;33(16):2715-8.
 Schlievert PM, et al. Glycerol monolaurate contributes to the antimicrobial and anti-inflammatory activity of human milk. Sci Rep. 2019 Oct 10;9(1):14550.
 Isaacs CE. The antimicrobial function of milk lipids. Adv Nutr Res. 2001;10:271-85.
 Thormar H, et al. Antimicrobial lipids: role in innate immunity and potential use in prevention and treatment of infections. In: Méndez-Vilas A, ed. Microbial Pathogens and Strategies for Combating Them: Science, Technology and Education (3). Badajoz, Spain: Formatex Research Center; 2013:1474-88.
 Sands JA, et al. Enveloped virus inactivation by fatty acid derivatives. Antimicrob Agents Chemother. 1979 Jan 1;15(1):134-6.
 Preuss SG, et al. Minimum inhibitory concentrations of herbal essential oils and monolaurin for gram-positive and gram-negative bacteria. Mol Cell Biochem. 2005 Apr;272(1-2):29-34.
 Lieberman S, et al. A review of monolaurin and lauric acid: natural virucidal and bactericidal agents. Altern Complement Ther. 2006 Dec 1;12(6):310-4.
 Strandberg KL, et al. Glycerol monolaurate inhibits Candida and Gardnerella vaginalis in vitro and in vivo but not Lactobacillus. Antimicrob Agents Chemother. 2010 Feb;54(2):597-601.
 Schlievert PM, Peterson ML. Glycerol monolaurate antibacterial activity in broth and biofilm cultures. PLoS One. 2012;7(7):e40350.
 Manohar V, et al. In vitro and in vivo effects of two coconut oils in comparison to monolaurin on Staphylococcus aureus: rodent studies. J Med Food. 2013 Jun;16(6):499-503.
 Batovska DI, et al. Antibacterial study of the medium chain fatty acids and their 1-monoglycerides: individual effects and synergistic relationships. Pol J Microbiol. 2009 Jan 1;58(1):43-7.
 Gänzle MG. Reutericyclin: biological activity, mode of action, and potential applications. Appl Microbiol Biotechnol. 2004 Apr;64(3):326-32.
 Hurdle JG, et al. Reutericyclin and related analogues kill stationary phase Clostridium difficile at achievable colonic concentrations. J Antimicrob Chemother. 2011 Aug;66(8):1773-6.
 Hierholzer JC, Kabara JJ. In vitro effects of monolaurin compounds on enveloped RNA and DNA viruses. J Food Safety. 1982 Mar;4(1):1-2.
 Plemper RK. Cell entry of enveloped viruses. Curr Opin Virol. 2011 Aug;1(2):92-100.
 Thormar H, et al. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987 Jan;31(1):27-31.
 Yoon BK, et al. Antibacterial free fatty acids and monoglycerides: biological activities, experimental testing, and therapeutic applications. Int J Mol Sci. 2018 Apr 8;19(4):1114.
 Kovanda L, et al. In vitro antimicrobial activities of organic acids and their derivatives on several species of gram-negative and gram-positive bacteria. Molecules. 2019 Oct 19;24(20):3770.
 Hess DJ, et al. The natural surfactant glycerol monolaurate significantly reduces development of Staphylococcus aureus and Enterococcus faecalis biofilms. Surg Infect (Larchmt). 2015 Oct;16(5):538-42.
 Morris DE, et al. Secondary bacterial infections associated with influenza pandemics. Front Microbiol. 2017 Jun 23;8:1041.
 Mo Q, et al. High-dose glycerol monolaurate up-regulated beneficial indigenous microbiota without inducing metabolic dysfunction and systemic inflammation: new insights into its antimicrobial potential. Nutrients. 2019 Aug 22;11(9):1981.
 Minodier L, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know? Virol J. 2015 Dec 12;12:215.
 Groves HT, et al. Respiratory disease following viral lung infection alters the murine gut microbiota. Front Immunol. 2018 Feb 12;9:182.
 Openshaw PJ. Crossing barriers: infections of the lung and the gut. Mucosal Immunol. 2009 Mar;2(2):100-2.
 Ichinohe T, et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5354-9.
 Li N, et al. The commensal microbiota and viral infection: a comprehensive review. Front Immunol. 2019 Jul 4;10:1551.