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Artemisia plants, prophylaxis and gut microbiota

March 8, 2016 - 08:11 -- Pierre Lutgen

The human gut microbiota has become the subject of extensive research in recent years and our knowledge of the resident species and their potential functional capacity is rapidly growing. Our gut harbours a complex community of over 100 trillion microbial cells which influence human physiology, metabolism, nutrition and immune function while disruption to the gut microbiota has been linked with many diseases. The gut microbiota exercise multiple functions such as metabolic activities (including fermentation); a barrier effect against pathogenic microorganisms; development and maturing of the immune system; effects on the movement and absorption of the colon; which all relate to physiological functioning.

The microbiota is also protective during specific disease conditions and is a major biotope indispensable in the maintenance of optimal digestive and immune functions. It therefore ought to be protected against any alteration of its equilibrium and can even be positively modulated to enhance protective effects. Higher level of Lactobacillus colonization diminishes the risk of having diarrhea. Diarrhea creates a shift in microbiota. In swine for example porcine endemic diarrhea reduces Lactobacillus by 50% (Hyeon-Woo Koh,et al Microbes Environ. 2015 Sep; 30 284–287). The results of a meta-analysis show that Lactobacillus is safe and effective for treating children with acute infectious diarrhea (CW Van Niel et al., Pediatrics, 2002, 109, 678-84). Several protector mechanisms have been proposed for Lactobacillus against gastroenteritis. The most likely mechanism is its role as immunomodulator. (AL Morrow, Protecting Infants through human Milk, 2004, Kluwer Acad.) Higher bottle feeding with milk poorer than breast milk in Lactobacillus increases the risk of diarrhea. In a trial probiotics Lactobacillus and Bifidobacterium shortened duration of diarrhea to 34.1hrs versus 58 hrs with placebo and reduced the number of stools (7.3 vs 15.9 with placebo). (S. Rerksuppaphol et al., Ann Trop Paediatr. 2010 Dec; 30(4): 299–304.)

Malaria changes the intestinal flora. Distinct gut microbiota have been found in southeasten African and northern European infants. Children from the malaria endemic country Malawia had a more abundant Lactobacillus microbiota with a richer Lactobacillus community and more diverse in the Malawian infants compared with Finnish infants (J Aako et al., J Pediatr Gastroenterol Nutr 2015, 61, 641-8). Bifidobacteria were dominant at 6 months of age in all infants, although in greater proportions in Malawian (71%) than Finnish infants (47%). The authors suggest this might be related to diet. It might also reflect on adaptation to malaria and gastrointestal infection and a strengthening of the immune system against these diseases.

THE CATASTROPHIC FAILURE OF CHEMICAL VACCINES

The development of a malaria vaccine has been a persistent and heavily funded goal now for over half a century, but to date not a single effective solution has been produced. This is all the more surprising when you consider the roster of powerful organizations presently invested in finding one:

- Bill and Melinda Gates Foundation (particularly through PATH Malaria Vaccine Initiative)

- The US National Institute for Allergy and Infectious Disease

- The European Union DG

- The United States Agency for International Development

- The Wellcome Trust - The Medical Research Council UK - The European Vaccine Initiative (formerly EMVI)

- The European and Developing Countries Clinical Trials Partnership

- The World Health Organization

These vaccines and their clinical trials have left a heavy death toll all over Africa

THE DAWN OF PLANT BASED PROBIOTIC VACCINES

An emerging area of study is the link between stomach bacteria and diseases that are, or may be, bacteria related. It has been shown that transferring gut bacteria from a person who has had malaria, to one who has not, provided a significant improvement in immunity to malaria in the subject. Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum (S Yooseph et al., BMC Genomics 2015, 16 :631). These findings underscore the diversity of gut microbiotica across geographic regions and suggest that strategic modulation of gut microbiota could decrease the risk of malaria.

Polyunsaturated fatty acids present in Artemisia also induce changes in surface properties of Lactobacilli and redirect the balance of inflammatory mediators (P Kankaanpäa et al., Appl Environment Microbiol. 2004 70, 129-136). Recently a Chinese team has shown that Artemisia sphaerulacta extracts, more than glucans, increase the gut bacterial diversity (J Zhang et al., Food Science, 2015, 36, 146-153. Artemisia is rich in polysaccharides, glycans and inulin. These were shown to protect mice from enteric and systemic pathogens (K Buddington et al., Nutritional Immunology, 29 Nov 2001). Iron supplements should be handled with caution. African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. And it is well known that iron supplements enhance the susceptibility to malaria infection (M.B Zimmerman et al., Am J Clin Nutr 2010, 92, 1406-15).

A recent study titled "Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission," (B Yilmaz et al., Cell, 2014, 159, 1277-1289) reveals that the human gut bacteria Escherichia coli , normally considered a microbe of pathogenic potential within the host, may help us fend off malaria infection. Host organisms recognize pathogen-associated molecular patterns, including glycans. During evolution, selective pressures for an effective human immune system result in genetic polymorphisms that prevent the biosynthesis of certain glycans, including Galα1-3Galβ1-4GlnAc-R (α-gal) in humans. Thus, human exposure to common α-gal-positive pathogens, including enterobacteria, such as Escherichia coli, induces the production of high titers of circulating antibodies against α-gal. The team from Portugal also found that Plasmodium falciparum expresses the same glycan molecule as E.coli. It is thus logical to expect that antibodies to α-gal cytotoxic to E.coli are also cytotoxic to Plasmodium. Anti-α-gal antibodies bind to the sporozoite surface, induce their lysis and prevent Plasmodium invasion of hepatic cells. In humans in Mali where malaria is an important health risk, the amount of IgG and IgM antibodies against α-gal increased with age. Young children do not produce enough anti-α-gal. It was also noticed that the average amount of antibodies against α-gal prior to the malarial season was greater in children who did not subsequently get the disease, compared to those that did. Thus, circulating antibodies against α-gal derived from exposure to common pathogens like E.coli may limit transmission of the parasites that cause malaria and immunization with α-gal may be an effective malaria prophylactic.

The recent findings from Portugal are in line with more ancient data. The University of Caracas (JL Avila et al., J Immunol 1989, 142, 2828-34) found that Trypanosoma and Leishmania parasites induce anti-α-gal in humans. Patients infected by these diseases have titers 10- and 16-fold higher than that of healthy individuals. It is argued that these antibodies may contribute to the natural defense against such parasites. In Sri Lanka it was shown that for catharrine monkeys anti-α-gal antibodies inhibit Plasmodium falciparum growth in culture (R Ramasamy et al.,Biochimica et Biophysica, 1997, 1360, 241-246). These naturally occurring antibodies are known to be the primary effectors of human hyperacute rejection of nonhuman tissue (K Posekany et al., Infection and Immunity, 2002, 70, 6215-22).

PATRICK OGWANG’S LANDMARK WORK ON PROPHYLAXIS

. Patrick Ogwang, the University of Makerere and the Ministry of Health in Uganda have developed a prophylactic drug composed of Artemisia, Avocado and Lemongrass. The prophylactic properties have been confirmed and documented in several in vivo trials with farm workers (P Ogwang et al., Tropical Journal of Pharmaceutical Research June 2012; 13 (3): 445-45),( P Ogwang et al., Brit J Pharmac Research 2011, 1, 124-131). These findings and papers were severely criticized by Merlin Willcox from Oxford. New ideas often trigger rejection. In science it is valid to question the findings of others as long as the questions deal with facts and not with dogmas

Patrick Ogwang’s findings on prophylaxis and transmission have been corroborated by several recent trials (data available on request). He will probably be recognized by medical history as a forerunner. Anyway the University of Makerere opened a new field of research. 

Lucile Cornet-Vernet

Pierre Lutgen