Dysbiosis – What Have We Learned?

Michael Ash BSc(Hons) DO, ND, FDipION reviews some of the last 12 months of published research.

The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing or never develops?

Plus what can we do to limit any adverse consequences linked to microbial disruption – referred to as dysbiosis?[1]

Further, do probiotics—dietary supplements containing potentially beneficial microbes actually support appropriate immune responses?

Not only do gut bacteria help protect against other disease-causing bacteria that might come from your food and water, they represent another arm of the immune system.

Recent Discoveries

What have we learnt in just the last few months about how we – humans and bacteria live and function together is starting to have a powerful impact in the way health care and disease management are being considered. The growing understanding of the role of our gastrointestinal bacteria in terms of health[2],[3] and disease[4],[5] through increasingly sophisticated analysis of genetics and bioinformatics is producing remarkable and novel insights. Many of these comfortably fit the nutritional and naturopathic ideologies we have been trained to embrace. The concept that the gut and its inhabitants may provide a key to health and disease is being taken ever more seriously by the scientific and clinical community.[6]

Antibiotics

Long suspected but mostly denied or pushed aside has been the view that even a single course of antibiotics may change the composition of our internal bacterial companions for months after the therapy. This is not just being recognised as a real event,[7],[8] but also it is understood how this can make an individual prone to intercurrent bacterial infections.[9] In much the same way, infections of the gastrointestinal tract can also have a profound effect on the composition of the commensal organisms,[10] both events of which can lead to a problem called dysbiosis. This condition may manifest in a variety of ways that compromises the local tissues and remote tissues, through a number of inflammatory proteins, molecular mimicry and parainflammation. The appropriate use of strain specific probiotics has shown success in the resolution of this complaint.[11]

There is an increasing weight of evidence that points to long-term chronic consequences of acute gastro intestinal infectious insults, including the development of a surprisingly common post infectious irritable bowel syndrome (IBS)[12]and inflammatory bowel diseases (IBD).[13]

Pathogens

An estimated 1400 human pathogens have been identified of which a remarkable 50% are zoonotic (a disease that can be transmitted from animals to people or, more specifically, a disease that normally exists in animals but that can infect humans) in origin, arising from coming into contact with creatures such as bats, ruminants (cows) and birds. A number approximating 177 are currently classified as emerging or re-emerging pathogens, but it is quite likely his number is too conservative.[14] In the main this is due to the complications linked to sample collection. A wide range of variables can affect the quality and accuracy of the sample contents, including timing of collection, the use of natural and pharmacological anti microbials or other growth inhibiting compounds, culture medium used and atmospheric conditions.

More importantly it is not yet possible to culture successfully all of the organisms that reside in the wet tissues of the body, and whilst sophisticated molecular techniques are available to the research centre – these are not yet available to normal pathology laboratories.[15],[16]

How do pro/pre-biotics fix dysbiosis?

Probiotic supplements may have a unique action of repair in dysbiosis by altering signalling mechanisms that have become disrupted due to the dysbiosis. A well understood proinflammatory cytokine called interferon gamma once activated switches on NF-κB (nuclear factor-kappa B) and in doing so activates over 500 genes used in the normal inflammatory defence process. Some probiotics (L. Helveticus) are able to stop this process, albeit they work better prophylactically rather than reactively at present.[17] Others (LGG) are better at restoring gut barrier function and so reducing translocation of inflammatory cells across the mucosal wall.[18]

As a result, beneficial microbes should now be considered for further evaluation as a potential agent restoration of dysbiosis and become part of an integrated strategy to correct local and systemic health issues connected to loss of function in the gastrointestinal tract.

Probiotics could well have a protective role in this clinical setting by acting to alter enteric neural and muscular dysfunction and the low-grade inflammatory responses that appear to mediate chronic IBS-related symptoms after an acute intercurrent bacterial infection often following exposure to a pathogen or post antibiotic therapy.[19]

Constituents of the commensal intestinal microbiota and exogenous agents, such as probiotics and prebiotics (defined as nondigestible oligosaccharides used as substrate in the colon by resident Bifidiobacteria and lactic acid-producing organisms), can both serve to restore gut homeostasis.[20]

Securil

A special type of probiotic bacteria found in food called Propionibacterium freudenreichii (PF), can simultaneously function as a prebiotic. They reproduce in the lower gut and generate prophylactic short-chain fatty acids (SCFA), including propionate and acetate. These SCFA lower the pH, protect the intestinal lining, down-regulate NF-κB (nuclear factor-kappa B), and support absorption of calcium, magnesium and potassium.[21]

Probiotics and selected prebiotics are gaining increasing attention as a novel approach to prevent intercurrent infections and dysbiosis and reduce both local and regional illness driven by loss of bacterial tolerance in the gastrointestinal tract.[22]

References

[1] Sartor, R. (2008). Therapeutic correction of bacterial dysbiosis discovered by molecular techniques Proceedings of the National Academy of Sciences, 105 (43), 16413-16414 DOI: 10.1073/pnas.0809363105

[2] Martin FP, Sprenger N, Yap IK, Wang Y, Bibiloni R, Rochat F, Rezzi S, Cherbut C, Kochhar S, Lindon JC, Holmes E, & Nicholson JK (2009). Panorganismal gut microbiome-host metabolic crosstalk. Journal of proteome research, 8 (4), 2090-105 PMID: 19281268

[3] Ley RE, Lozupone CA, Hamady M, Knight R, & Gordon JI (2008). Worlds within worlds: evolution of the vertebrate gut microbiota. Nature reviews. Microbiology, 6 (10), 776-88 PMID: 18794915

[4] Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology 2009; 136:65–80 View Abstract

[5] Zhang H, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci (USA) 2009; 106:2365–2370. View Abstract View Full Paper

[6] Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease.Nat Rev Immunol. 2009 May;9(5):313-23. View Abstract

[7] Antonopoulos DA, Huse SM, Morrison HG, et al. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic pertubation. Infect Immun 2009; 77:2367–2375. View Abstract

[8] Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 2008; 6:e280. View Abstract

[9] Crosswell A, Amir E, Teggatz P, et al. Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection. Infect Immun 2009; 77:2741–2753.View Abstract

[10] Monira S, Alam NH, Suau A, et al. Time course of bacterial diversity in stool samples of malnourished children with cholera receiving treatment. J Pediatr Gastroenterol Nutr 2009; 48:571–578. View Abstract

[11] Sherman PM, Ossa JC, Johnson-Henry K. Unravelling mechanisms of action of probiotics. Nutr Clin Pract 2009; 24:10–14. View Abstract

[12] Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology 2009; 136:1979–1988View Abstract

[13] Ternhag A, Torner A, Svensson A, et al. Short- and long-term effects of bacterial gastrointestinal infections. Emerg Infect Dis 2008; 14:143–148. View Abstract

[14] Woolhouse ME, Gowtage-Sequeria S. Host range and emerging and reemerging pathogens. Emerg Infect Dis 2005; 11:1842–1847. View Abstract

[15] Finkbeiner SR, Allred AF, Tarr PI, et al. Metagenomic analysis of human diarrhea: viral detection and discovery. PLoS Pathogens 2008; 4:39–47. View Abstract

[16] Palacios G, Druce J, Du L, et al. A new arena virus in a cluster of fatal transplant-associated diseases. N Engl J Med 2008; 358:991–998. View Abstract

[17] Jandu N, Zeng ZJ, Johnson-Henry KC, Sherman PM. Probiotics prevent enterohaemorrhagic Escherichia coli O157:H7-mediated inhibition of interferon-γ-induced tyrosine phosphorylation of STAT-1. Microbiology UK 2009; 155:531–540. View Abstract

[18] Johnson-Henry KC, Donato KA, Shen-Tu G, et al. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect Immun 2008; 76:1340–1348. View Abstract

[19] Verdu EF. Probiotics effects on gastrointestinal function: beyond the gut? Neurogastrointest Motil 2009; 21:477–480. View Abstract

[20] Ventura M, O’Flaherty S, Claesson MJ, et al. Genome-scale analyses of health-promoting bacteria: probiogenomics. Nat Rev Microbiol 2009; 7:61–71. View Abstract

[21] Kaneko T, Mori H, Iwata M, and Meguro S. Growth stimulator for Bifidobacteria produced by Propionibacteria freudenreichii and several intestinal bacteria. J Dairy Sci. 1994; 77:393-404. View Abstract

[22] Wells JM, Mercenier A. Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat Rev Microbiol 2008; 6:349–362. View Abstract

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Responses

5 Responses to “Dysbiosis – What Have We Learned?”

  • Sandra says:

    Is Securil safe for a 4 year old?

    • Michael Ash says:

      Sécuril® is a novel formulation designed to naturally support intestinal health. It contains a special type of probiotic bacteria found in food called Propionibacterium freudenreichii, which can simultaneously function as a prebiotic. Yhis bacteria may be consumed by a child safely, the suggested dose for a normal sized 4 year old would be one per day.

  • Tara Zenker says:

    Would this be appropriate for an 18-week old infant whose gut has been severely compromised by mother taking antibiotics and other drugs during C Section? I’m concerned about giving probiotics without having given prebiotics beforehand to prepare her gut? Infant can’t tolerate milk, not even breast milk and in pain on feeding still.

    • Michael Ash says:

      Hello Tara
      Prebiotics do appear based on a number of studies to aid in the metabolic and immunological benefits of a probiotic. In very immature gastric tracts the use of probiotics is less well understood. There is good evidence for the reduction and in some cases the resolution of necrotising enterocolitis, but may I suggestthat you consider the utilisation of a small amount of colostrum presented as a spray that may be added to tolerated food, placed onto a clean finger for sucking or onto the nipple as and when feeding may commence. The product cytolog is capable of delivering the active agent – made by allergy research group.

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  1. […] immune response in the intestines is also changed. This altered host–microbe relationship, called dysbiosis, has been linked to IBD and colon cancer as well as to obesity and diabetes and other inflammatory […]



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