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Reshaping your gut from the inside out

The takeaway

  • Removing detrimental bacteria is the first cornerstorne of The Microbiome Diet

  • The Microbiome Diet recommends using berberine, garlic or a combination of berberine, garlic, wormwood, caprylic acid, grapefruit seed extract and oregano oil to kill bad bacteria

  • The human gut contains four main groups (phyla) of bacteria: Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria

  • High fat diets and/or obesity are associated with unbalanced microbiota, often increased Firmicutes and decreased Bacteroidetes

  • Antimicrobial supplements may help “reset” the gut especially when used with improved eating habits including probiotics and prebiotic fiber.

The aim of the Microbiome Diet is to restore the balance in the gut microbiota and heal the gut. That means promoting the growth of the beneficial microbes, removing the detrimental one. As I reviewed in an earlier post, the first cornerstone of The Microbiome Diet is to “Remove detrimental bacteria and the food that supports its growth.”

For the first 3 weeks of the Microbiome Diet, Dr. Kellman recommends using one of the following supplements:

  • Berberine OR

  • Garlic extract OR

  • A combination supplement containing berberine, garlic, wormwood, caprylic acid, grapefruit seed extract and oregano oil.

*Genus and species of plant source

Most of you probably don’t love the idea of taking pills, and I don’t either. But I am committed to overhauling my gut and eating habits, so I put my reservations aside, and decided to take The Microbiome Diet-recommended supplements (there are many other supplements that will be discussed in a later post).

One caveat that I considered is that the supplements discussed here are general antimicrobials, meaning they will likely kill a variety of species in the gut. In general, more diversity is better in terms of gut microbes. So I plan to stick with the recommended 3 week course of one the antimicrobial supplements (I chose to take berberine, for reasons I explain at the end of the article). I figure that taking the supplement, along with eating an improved diet full of nutrients, probiotics and prebiotic fiber will encourage a beneficial shift in the gut bacteria.

Note: The Microbiome Diet also recommends taking probiotics. To get the full benefit of a probiotic, I recommend taking the antimicrobial pill (berberine, garlic, or combo) in the morning and the probiotic before bed. I don’t have information regarding metabolism of these supplements, but in general medications will peak in the bloodstream within a few hours of ingestion. Timing the probiotic after the peak means that the bacteria in the probiotic pill have a better chance of colonizing the gut.

When I started the Microbiome Diet, I had a few questions:

  • Which microbes live in the gut?

  • How are gut microbes involved in weight gain?

  • What effect will these supplements have on my ‘crobes?

Let’s start at the beginning.

Characterization of the microbiome in healthy individuals has shown that adults typically harbor over 1000 species of bacteria, predominantly from the phyla (see side box) Firmicutes and Bacteroidetes [25]. Members of the phyla Proteobacteria and Actinobacteria comprise a lesser but still substantial proportion of the microbiome, and Verrucomicrobia, Fusobacteria and TM7 phyla account for a minor portion. [26]. The gut also contains archaea, fungi, protozoa and bacteriophages (viruses that infect bacteria), but bacteria make up the majority and are the most extensively studied gut microbiota.

Although family members will share some species, each person’s gut microbial community is unique. In fact, in a study of monozygotic and dizygotic twins and their mothers, there was not a single abundant species (<0.5% of the microbiota) shared by all 154 individuals [27].

Interestingly, researchers have found that while microbes vary substantially between people, the microbiomes converge on a functional level [27, 28]. The actual microbes present may vary, but the genes they carry are similar. The term microbiome refers to the genomes and genes carried by the microbiota, so the gut microbiome represents the cellular functions the gut microbes are capable of performing.

One function microbes contribute is energy harvest. Mice maintained in a germ-free environment that harbored no gut microbes gained less weight than the same mice that were colonized with gut microbiota. Interestingly, the colonized mice, which gained less weight, actually ate less food [29]. This suggests that the gut microbes digest food that would otherwise go undigested, increasing the amount of energy available to the mice.

The story gets a bit more complicated when considering that germ-free mice gained more weight consuming a high fat diet than normal mice on the same diet [30]. This suggests that gut microbes may protect against the inflammatory effect of a high-fat diet. So while we know that caloric intake and energy expenditure affect weight gain, these studies suggest that the gut microbes also play key roles in weight gain.

Similarly, gut microbes are linked to obesity. Obesity is a complex condition influenced by genetic, environmental, neural and endocrine factors [31] and recent studies have challenged our conventional understanding about obesity. It’s not simply calories in, calories out. A study showed that mice fed the same diet gained different amounts of weight depending on the origin of their gut microbes. Germ-free mice colonized with gut microbes from obese mice gained substantially more weight while fed a standard diet than mice colonized with gut microbes from lean mice, also eating a standard diet [32]. This study suggests that gut microbes directly influence weight gain.

To better understand how microbes influence weight gain, several studies have compared the microbial communities of obese and lean people. Obese people had lower levels of Bacteroidetes and high levels of Firmicutes than did lean people [33]. Furthermore, Bacteroidetes increased and Firmicutes decreased in response to fat- or calorie-restricted diets [33]. In another study, Bacteroides and Lactobacillus (a Firmicute) increased in overweight adolescents after intervention with calorie restriction and increased exercise [34].

It has been proposed that Firmicutes extract more calories from food, thus harvesting more energy from the same number of calories [32, 35]. However, other studies have found conflicting results, linking increased Bacteroidetes with obesity and showing a reduction of Bacteroidetes during weight loss [31]. As is usually the case in scientific research, the answer is more complicated than initially appreciated and will require more studies to delineate.

Additional studies are shedding more light on the role of gut microbes in weight management. A review of recent literature showed that depletion of bacteria in the genus Bifidobacterium was consistently associated with obesity [31]. Researchers postulated that it may be a reduction in Bifidobacterium and concomitant increase in another genus such as Clostridium that contributes to obesity [34].

Maintaining proper balance of gut microbes helps ameliorate the negative effects of a high-fat diet. A series of studies from the Cani lab demonstrates the links between gut microbes, metabolic disease and obesity:

  • LPS is responsible for the onset of metabolic disease [36]

  • LPS is major component of outer membrane of Gram-negative bacteria

  • High fat diet caused an increase in Gram-negative to Gram-positive bacteria [37]

  • Dietary fiber normalized the ratio of Gram-negative to Gram-positive bacteria [37] increased bifidobacterium

  • Dietary fiber reduced the impact of the high-fat diet on occurrence of metabolic disease [38]

  • Altering the gut microbiota (using antibiotics) of mice fed a high-fat diet reduced intestinal permeability and decreased the endotoxin release [39]

  • Modulation of gut bacteria on a high-fat diet increases intestinal permeability by reducing the expression of genes encoding tight junctions [39]

Note: The use of antibiotics in this experiment demonstrates that gut bacteria are responsible for the effects; it does NOT suggest that people take antibiotics to lose weight or reverse metabolic disorders.

These studies DO support the notion altering the gut microbiota using antimicrobial supplements (such as those discussed in this post), eating a healthy diet containing prebiotic fiber, and introducing healthy bacteria through probiotics and fermented food can benefit our health.

A typical use for berberine is as an antibiotic to treat diarrhea, but it has also been used in Chinese medicine for hundreds of years to treat diabetes. To better understand how it treats diabetes, researchers performed a double-blind, randomized, placebo-controlled trial in which patients with Type II diabetes took 0.5 g of berberine twice daily for 3 months [2]. Berberine treatment significantly reduced fasting and postprandial (after meal) blood glucose levels, increased insulin sensitivity and lowered total cholesterol, LDL and triglyceride levels. It also regulates metabolic hormones [3]. A few cases of mild constipation occurred which were reversed by lowering the dose. Overall berberine was shown to effectively and safely treat Type II diabetes [2].

The effect of berberine may be due to its ability to alter the community of gut microbes. In mice, a high fat diet promoted the growth of certain bacteria (Firmicutes and Bacteroidetes in one study [40] and Actinobacteria and Verrucomicrobia in another [1]. But treatment with berberine restored the balance. Thus, using berberine may help offset some of the negative changes that occur in the gut due to a high-fat diet.

The effect of garlic on the gut microbiome has not been evaluated, but it has been tested with a few representative species of but bacteria grown in pure culture in the lab. While these conditions do not at all reflect the environment of the gut, they may give us some clues as to how garlic could work. The study found that a strain of Lactobacillus was essentially resistant to the garlic, whereas other bacteria found in the gut such as Bacteroides, Bifidobacterium and Clostridium were killed rapidly [41].

Caprylic acid is a medium-chain saturated fatty acid. A mixture of medium-chain fatty acids, including caprylic acid, fed to piglets increased the abundance of certain types of bacteria, including Enterobacteriaceae, Clostridium, and two strains of Lactobacillus johnsonii and Lactobacillus amylovorus [42]. This study shows that ingestion of medium-chain fatty acids can modulate the bacterial communities in the gut.

I couldn’t find any studies that evaluated the effect of the other supplements on gut microbiota, weight gain, or the like. I consider the information I did find to be fairly limited, unfortunately there aren’t more studies assessing the effect of herbal/natural supplements on the gut microbiota. But based on the available knowledge, I chose to take berberine over garlic and the combination supplement. I considered the combo pill but struggled to find something that contained all six extracts. I eat quite a bit of garlic so I decided against taking it in pill form. Since berberine can help regulate blood sugar and insulin sensitivity, it seemed like it offered the greatest health benefits.

Do you take any of these or other supplements intended to alter gut microbiota? Have you ever noticed a change in body composition or digestion after using antibiotics?

References

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  2. Zhang, Y., et al., Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab, 2008. 93(7): p. 2559-65.

  3. Xu, J.H., et al., Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol Med Rep, 2017. 15(5): p. 2765-2787.

  4. Elnima, E.I., et al., The antimicrobial activity of garlic and onion extracts. Pharmazie, 1983. 38(11): p. 747-8.

  5. Sharifi-Rad, J., et al., Plants of the genus Allium as antibacterial agents: From tradition to pharmacy. Cell Mol Biol (Noisy-le-grand), 2016. 62(9): p. 57-68.

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  11. Kim, S.A. and M.S. Rhee, Use of caprylic acid to control pathogens (Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium) in apple juice at mild heat temperature. J Appl Microbiol, 2015. 119(5): p. 1317-23.

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  13. Hulankova, R., G. Borilova, and I. Steinhauserova, Combined antimicrobial effect of oregano essential oil and caprylic acid in minced beef. Meat Sci, 2013. 95(2): p. 190-4.

  14. Jadhav, A., et al., The Dietary Food Components Capric Acid and Caprylic Acid Inhibit Virulence Factors in Candida albicans Through Multitargeting. J Med Food, 2017.

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  17. Reagor, L., et al., The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay. J Altern Complement Med, 2002. 8(3): p. 325-32.

  18. Kanmani, P. and J.W. Rhim, Development and characterization of carrageenan/grapefruit seed extract composite films for active packaging. Int J Biol Macromol, 2014. 68: p. 258-66.

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  20. Friedman, M., P.R. Henika, and R.E. Mandrell, Bactericidal activities of plant essential oils and some of their isolated constituents against Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. J Food Prot, 2002. 65(10): p. 1545-60.

  21. Force, M., W.S. Sparks, and R.A. Ronzio, Inhibition of enteric parasites by emulsified oil of oregano in vivo. Phytother Res, 2000. 14(3): p. 213-4.

  22. Gomez-Mateos Perez, M., et al., Evaluation of different Mediterranean essential oils as prophylactic agents in anisakidosis. Pharm Biol, 2017. 55(1): p. 456-461.

  23. Kwon, S.J., Y. Chang, and J. Han, Oregano essential oil-based natural antimicrobial packaging film to inactivate Salmonella enterica and yeasts/molds in the atmosphere surrounding cherry tomatoes. Food Microbiol, 2017. 65: p. 114-121.

  24. Skandamis, P.N. and G.J. Nychas, Effect of oregano essential oil on microbiological and physico-chemical attributes of minced meat stored in air and modified atmospheres. J Appl Microbiol, 2001. 91(6): p. 1011-22.

  25. Eckburg, P.B., et al., Diversity of the human intestinal microbial flora. Science, 2005. 308(5728): p. 1635-8.

  26. Lozupone, C.A., et al., Diversity, stability and resilience of the human gut microbiota. Nature, 2012. 489(7415): p. 220-30.

  27. Turnbaugh, P.J., et al., A core gut microbiome in obese and lean twins. Nature, 2009. 457(7228): p. 480-4.

  28. Shreiner, A.B., J.Y. Kao, and V.B. Young, The gut microbiome in health and in disease. Curr Opin Gastroenterol, 2015. 31(1): p. 69-75.

  29. Backhed, F., et al., The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A, 2004. 101(44): p. 15718-23.

  30. Fleissner, C.K., et al., Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr, 2010. 104(6): p. 919-29.

  31. Angelakis, E., et al., The relationship between gut microbiota and weight gain in humans. Future Microbiol, 2012. 7(1): p. 91-109.

  32. Turnbaugh, P.J., et al., An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 2006. 444(7122): p. 1027-31.

  33. Ley, R.E., et al., Microbial ecology: human gut microbes associated with obesity. Nature, 2006. 444(7122): p. 1022-3.

  34. Santacruz, A., et al., Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring), 2009. 17(10): p. 1906-15.

  35. Jumpertz, R., et al., Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr, 2011. 94(1): p. 58-65.

  36. Cani, P.D., et al., Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 2007. 56(7): p. 1761-72.

  37. Cani, P.D., et al., Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia, 2007. 50(11): p. 2374-83.

  38. Cani, P.D., et al., Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes, 2006. 55(5): p. 1484-90.

  39. Cani, P.D., et al., Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 2008. 57(6): p. 1470-81.

  40. Xie, W., et al., Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One, 2011. 6(9): p. e24520.

  41. Filocamo, A., et al., Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract. Phytomedicine, 2012. 19(8-9): p. 707-11.

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Welcome

I believe opinions should be stated with scientific support. I believe through deeper understanding we can influence not just our habits, but our health and well-being. I believe it’s our responsibility to educate and ensure knowledge is appreciated.

So welcome to my blog. I’ll take you through my journey of discovery. Starting with commonplace ideas or beliefs, I’ll identify the underlying assumptions and search through scientific rigor for the truth.

You’ll learn about interesting topics like the gut microbiome, bacteria we encounter, infections and hygiene to mention a few. I’m sure this list will grow as we build our future together.

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