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How the Microbiome Helps Protect Us from Gut Infections

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VIDEO LENGTH: 50 minutes

Summary Points

  • New research is revealing that gut pathogens can cause long-term health issues, even when the pathogens are completely eliminated
  • Gut infections caused by pathogens can lead to persistent dysbiosis and inflammation
  • The gut microbiome helps counteract pathogens and pathobionts through a process called colonization resistance
  • The gut microbiome also interacts extensively with components of the mucosal barrier, and together they constitute a major defense system agains pathogen invasion
  • A number of factors, such as antibiotics, can disrupt the microbiome and mucosal barrier, leading to an increased risk of infection
  • New research suggests that a multifactorial approach to support a healthy microbiome and mucosal barrier (such as diet, supplements, and lifestyle factors) may help to reduce pathogen and pathobiont infections of the gut

Gut Pathogens & Dysbiosis MasterClass

This online class begins October 17th, 2016
In this MasterClass, we will go into much greater depth on the topics that are covered briefly in this video update.

DETAILS & REGISTRATION

Microbiome Update #2: How Does Berberine Affect the Microbiome?

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VIDEO LENGTH: 27 minutes

Berberine has attracted a lot of attention recently, especially as a potential treatment for for SIBO, gastrointestinal infections, and metabolic disorders such as diabetes. Berberine’s health effects are likely mediated by the microbiome, and berberine is also known to affect the microbiome.

Watch this edition of Microbiome Update to learn what’s currently known about how berberine impacts the microbiome, and what implications this influence may have on health.

Summary Points

  • Gut bacteria can convert berberine into a more absorbable form, increasing its bioavailability
  • Berberine has a large impact on the microbiome:
    • Large initial reduction overall, by inhibiting bacterial cell division
    • Negative effect on many potential pathogens: Proteobacteria (E. coli, Shigella, Salmonella, Klebsiella, Proteus, Vibrio), Staphylococcus, etc.
    • Increases the relative proportion of some key beneficial groups: Clostridia (butyrate producers), Bifidobacteria, possibly Lactobacilli
  • Berberine can also inhibit Candida and other potential opportunistic pathogens and parasites
  • Berberine cautions:
    • It can cause an initial broad-spectrum reduction in microbiome, similar to antibiotics
    • It may reduce the overall diversity of the microbiome, also similar to antibiotics
  • The effects of berberine likely to be very individual:
    • The microbiome composition (degree of dysbiosis) varies among individuals, so berberine is likely to have differing effects depending on these inter-individual differences

MICROBIOME UPDATE #1: Autoimmunity & IBD

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Welcome to the first edition of the MICROBIOME UPDATE, which will be an ongoing series on this blog (as well as in my newsletter, MM News). In each edition, we will briefly highlight recently-published research articles – and occasionally quality articles from the popular media – that highlight important advances in our understanding of the microbiome and its role in health. Many of the editions will focus on a particular topic, so you can quickly get up-to-date on recent developments within that topic area.

So, without further ado, here is the first edition:

EDITION TOPIC: Autoimmunity and Inflammatory Bowel Disease

Lactobacillus acidophilus suppresses colitis-associated activation of the IL-23/Th17 axis

This study used a mouse model of chemically-induced colitis to evaluate the effects of a probiotic strain (Lactobacillus acidophilus SMC-S095) on a key pathway involved in the pathogenesis of colitis (the IL-23/Th17 pathway). They found that L. acidophilus SMC-S095 was able to suppress key components of the pathway, suggesting that this probiotic strain may prove to be useful for treating at least some inflammatory bowel diseases. Studies in humans are needed in order to verify the effectiveness of this strain.
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Th17 cells in Type I diabetes: Role in the pathogenesis and regulation by gut microbiota

This article summarizes what’s currently known about the critical role of Th17 cells and the microbiome in Type I diabetes. Th17 cells were only recently recognized, but are now thought to play a critical role in a wide variety of autoimmune and inflammatory disorders, so it’s well worth spending some time getting to know this type of T helper cell. For example, Th17 cells are though to play a role in normal intestinal homeostasis, but when Th17 responses are excessive or insufficient (possibly due to dysbiosis), they may play a role key role in certain diseases.
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Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses

This study examined the effect of berberine in a mouse model of chronic relapsing ulcerative colitis. Berberine improved several measures of disease severity, and had an especially strong effect in suppressing Th17-related responses, including inflammatory cytokine gene expression, providing support for exploring the use of berberine in ulcerative colitis in humans.
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Oral probiotic VSL#3 prevents autoimmune diabetes by modulating microbiota and promoting indoleamine 2,3-dioxygenase-enriched tolerogenic intestinal environment

This study used a mouse genetic model that is prone to developing Type 1 diabetes to show that the probiotic VSL#3 prevented the development of the disease. They went on to show that VSL#3 appeared to work in part by reducing a key inflammatory cytokine (IL-1 beta) and increasing immune tolerance. These VSL#3-induced changes resulted in reduced levels of Th1 and Th17 cells, which have been linked to many autoimmune diseases.
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Interaction of intestinal microorganisms with the human host in the framework of autoimmune diseases

This review article discusses the role of the microbiome in systemic lupus erythematosus – an autoimmune disease. The article focuses on what is known about the role of dysbiosis, where specific changes in the composition of the microbiome may contribute to the disease via interaction with specific receptors on cells in the intestinal mucosa. They also discuss the possible role of molecular mimicry, superantigens (a group of toxins produced by many bacteria as well as viruses), and other potential ways they microbiota may contribute to autoimmune disease. Lastly, they discuss some ways in which dietary components and supplements (e.g., fiber, certain polyphenols, and probiotics) may improve autoimmune conditions by increasing Treg cells, which suppress other T helper cells (e.g., Th1, Th17) that are implicated in autoimmune conditions.
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Low-dose naltrexone: The new treatment you’ve never heard of

This recent blog post from Dr. Jill Carnahan discusses the use of low-dose naltrexone for a range of autoimmune and inflammatory disorders. At the end of the post is a video in which Dr. Carnahan discusses low-dose naltrexone in an interview.
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The Importance of Bile Acids, Part Two

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Motility and Health of the Intestinal Lining

As we saw above, bile acids can have a large impact on gut microbiota. But gut bacteria also have an impact on bile acids; the interaction is two-way. Different types of gut bacteria produce enzymes that can modify bile acids in different ways, producing what are called secondary bile acids. Some of these actions take place in the small intestine, while others take place in the colon.

A recent study showed that in mice, some species of Clostridia (a group of bacteria that was highlighted in the last issue of this newsletter) increased serotonin synthesis in enterochromaffin cells of the colon, resulting in faster intestinal transit rates. The researchers found that this effect was due to a secondary bile acid (deoxycholic acid, or DCA) produced by these Clostridia. This suggests that normal gut motility depends upon sufficient bile and sufficient amounts of Clostridia species to enable the conversion to DCA, and that too little – or too much – of either bile or Clostridia might contribute to constipation or diarrhea.

Another recent study showed that colonic bacteria can also promote motility via the production of short-chain fatty acids (SCFAs, which are produced by gut bacteria from fermentable carbohydrates). In this study, SCFAs were shown to also promote the production of serotonin in enterochromaffin cells.

Bile acids also play a role on fostering a healthy intestinal mucosal lining. As discussed above, one way that contribute to a healthy intestinal lining is by helping to control the growth and composition of the gut microbiota, but they can also promote intestinal health in other ways, via bile acid receptor signaling. Bile acid signaling via these receptors regulates the expression of genes involved in the integrity of the intestinal lining. Interestingly, in this study, they showed that licorice root extract containing glycyrrhizic acid could activate one of the bile acid receptors and promote the health of the stomach lining (licorice root extracts have been used to promote healing from peptic ulcers).

A Final Note on Bile Acids

The biological roles of bile acids and their derivatives is very complex and there is still much to be learned as their roles in health and dysfunction are clarified. It should be noted that bile acids and their derivatives can also have negative effects, such as promoting damage to intestinal cells at high concentrations (or in cases where the mucosal lining is already compromised by other factors). Some of the secondary bile acids produced by gut bacteria have also been linked to colon cancer. However, we still have a lot to learn about the conditions under which bile acids are beneficial vs. potentially harmful. As with most things in biology, too little or too much may increase the risk of harmful effects.

REFERENCES

The Importance of Bile Acids: Part One

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It may come as a surprise, but bile acids play many important roles when it comes to the microbiome, gastrointestinal health, metabolism, and a number of other physiological functions. This issue of the BIG Microbiome newsletter is dedicated to highlighting a few of these critical roles, including:

  • Helping to keep gut bacteria in check and preventing small intestinal bacterial overgrowth
  • Helping to maintain the integrity and health of the intestinal mucosal barrier
  • Playing a key role in gut motility via the stimulation of serotonin synthesis in the colon by certain bacteria and their metabolic products

Keeping Gut Bacteria in Check

Bile acids are released into the duodenum to help emulsify fats and facilitate the action of pancreatic lipase. Most bile acids (roughly 95%) are then reabsorbed further along the small intestine (in the ileum), and then transported via the portal vein back to the liver.

But the importance of bile acids in the small intestine does not end there – there is much more to the story. Bile acids also have a major effect on gut bacteria. Their detergent-like action that is so helpful for emulsifying fats can also disrupt bacterial membranes. Many types of bacteria are sensitive bile acids, and this is one reason why the concentration of bacteria is relatively low throughout most of the small intestine (in healthy people).

When bile levels are low (e.g. from an obstruction in the bile duct), bacteria can overgrow in the small intestine, which in turn can result in increased levels of circulating endotoxin (also called lipopolysaccharide  or LPS), which is a component of the cell wall of gram-negative bacteria. Elevated levels of endotoxin can cause increased systemic inflammation.

Experimental administration of bile acids has been shown to reduce small intestinal bacterial overgrowth (SIBO) in a rat model, but it is not yet clear if this approach will be beneficial for people with SIBO. However, the research does suggest that ensuring healthy liver function and consuming adequate fats (which stimulate bile release) may be important factors in maintaining normal levels of bacteria in the small intestine.

A second way in which bile acids may help to keep bacterial populations in check in the small intestine is via bile acid receptor signaling. There are receptors for bile acids on intestinal epithelial cells, and these receptors participate in signaling pathways that influence metabolism as well as some aspects of the immune response. One type of immune response that is activated by bile acids via receptor signaling is the production of antimicrobial peptides, which can also contribute to controlling bacterial populations.

A recent study showed that bile acids are also key in helping to protect against Clostridium difficile infection – by a complex mechanism that involves a non-pathogenic species of Clostridium (Clostridium scindens).

Together, the detergent activity of bile acids, the production of antimicrobial peptides by bile acid signaling, and the control of pathogens all function in helping to maintain healthy bacterial populations in the small intestine.

REFERENCES

DISCLAIMER

The information on this website is for educational purposes only. This information is not intended to be used to diagnose, treat, cure, or prevent any disease or medical condition, nor is it intended to be a substitute for professional medical advice. Always seek the advice of a licensed, qualified healthcare practitioner before acting upon any information provided herein.

© 2024, Thomas Fabian, PhD
MicrobiomeMastery.com

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