Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.

References

Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5. doi: 10.1016/j.appet.2011.01.016. Epub 2011 Jan 19.

Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB.
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.
Cell Host Microbe. 2012 Nov 15;12(5):611-22.

Beaugerie L, Petit JC.
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea.
Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):337-52.

Bischoff SC.
‘Gut health’: a new objective in medicine?
BMC Med. 2011 Mar 14;9:24.

Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS, Frokiaer H, Heinrich J, Garn H, et al
Early nutrition and immunity – progress and perspectives.
Br J Nutr. 2006 Oct;96(4):774-90.

Roberto Berni Canani, Margherita Di Costanzo, and Ludovica Leone
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Clin Epigenetics. 2012; 4(1): 4.

Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, et al
PASSCLAIM–gut health and immunity.
Eur J Nutr. 2004 Jun;43 Suppl 2:II118-II173.

de Vrese M, Schrezenmeir J.
Probiotics, prebiotics, and synbiotics.
Adv Biochem Eng Biotechnol. 2008;111:1-66. doi: 10.1007/10_2008_097.

Fanaro S, Chierici R, Guerrini P, Vigi V.
Intestinal microflora in early infancy: composition and development
Acta Paediatr Suppl. 441: 48-55. 2003

Flint HJ, Scott KP, Louis P, Duncan SH.
The role of the gut microbiota in nutrition and health.
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):577-89.

Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP, Sanderson IR.
Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.
Mol Med. 1999 Sep;5(9):631-40.

Gamet L, Daviaud D, Denis-Pouxviel C, Remesy C, Murat JC.
Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29.
Int J Cancer. 1992 Sep 9;52(2):286-9.

Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A.
Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota.
World J Gastroenterol. 2012 Dec 14;18(46):6693-700. doi: 10.3748/wjg.v18.i46.6693.

Guarner F, Malagelada JR.
Gut flora in health and disease.
Lancet. 2003 Feb 8;361(9356):512-9.

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, et al
The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.
Diabetes Obes Metab. 2012 Feb;14(2):112-20.

Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.
PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240. Epub 2012 Apr 10.

Macfarlane S, Macfarlane GT.
Regulation of short-chain fatty acid production.
Proc Nutr Soc. 2003 Feb;62(1):67-72.

MacFarlane, George T. and McBain, Andrew J. (2010). The Human Colonic Microbiota. In Colonic Microbiota, Nutrition and Health. Glenn Gibson, Ed. Dordrecht, the Netherlands: Kluwer Academic Publishers; pp 1-25

Martin FP, Dumas ME, Wang Y, Legido-Quigley C, Yap IK, Tang H, Zirah S, Murphy GM, et al
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
Mol Syst Biol. 2007;3:112.

Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, et al
Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
Mol Syst Biol. 2008;4:157.

Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S.
Host-gut microbiota metabolic interactions.
Science. 2012 Jun 8;336(6086):1262-7.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Omaida C. Velázquez MD, Howard M. Lederer MD, Dr. John L. Rombeau MD
Butyrate and the colonocyte
Digestive Diseases and Sciences. April 1996, Volume 41, Issue 4, pp 727-739

Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, et al
Prebiotic effects: metabolic and health benefits.
Br J Nutr. 2010 Aug;104 Suppl 2:S1-63.

Schwiertz A, Gruhl B, Löbnitz M, Michel P, Radke M, Blaut M.
Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants.
Pediatr Res. 2003 Sep;54(3):393-9. Epub 2003 Jun 4.

Scott KP, Duncan SH, Louis P, Flint HJ.
Nutritional influences on the gut microbiota and the consequences for gastrointestinal health.
Biochem Soc Trans. 2011 Aug;39(4):1073-8.

Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH.
The influence of diet on the gut microbiota.
Pharmacol Res. 2012 Nov 9. pii: S1043-6618(12)00207-1.

Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M.
Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.
Gastroenterology. 2010 May;138(5):1772-82.

Tsai F, Coyle WJ.
The microbiome and obesity: is obesity linked to our gut flora?
Curr Gastroenterol Rep. 2009 Aug;11(4):307-13.

Vedantam G, Hecht DW.
Antibiotics and anaerobes of gut origin.
Curr Opin Microbiol. 2003 Oct;6(5):457-61.

Yin L, Laevsky G, Giardina C.
Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity.
J Biol Chem. 2001 Nov 30;276(48):44641-6. Epub 2001 Sep 25.

Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S.
Destructive effects of butyrate on the cell envelope of Helicobacter pylori.
J Med Microbiol. 2012 Apr;61(Pt 4):582-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

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