Assessing Gut Issues: Short Chain Fatty Acids...Predominant gut bacteria ferment dietary fiber and their monosaccharide components to acetate, propionate, and butyrate, and protein

Assessing Gut Issues: Short Chain Fatty Acids

Elizabeth Redmond, PhD, MMSc, RD Chair-Elect Dietitians in Integrative and Functional Medicine DPG Education Specialist, Metametrix Laboratory, Georgia

Short Chain Fatty Acids (SFCA) This session will discuss: 1. What are SCFA ? 2. What do SCFA do? 3. What affects SCFA production? 4. Review of the synergistic relationship of SCFAs and gut bacteria. 5. Possible treatments and case study.

Presenter

Presentation Notes

Evidence for the health promoting characteristics of SCFA originates from epidemiological studies. Beneficial effects of SCFA have, however, mainly been described in animal and in vitro studies and relatively little studies have evaluated the direct health promoting effects of these SCFA in humans. Human studies with SCFA have all been carried out in patients with active intestinal inflammation and mainly deal with clinical parameters (chapter 2). So far no studies have investigated the local effects of SCFA in the healthy or mildly disturbed colon, while healthy subjects or individuals with chronic mild intestinal complaints comprise an important target group for functional foods.

Putrefactive SCFA

Predominant gut bacteria ferment dietary fiber and their monosaccharide components to acetate, propionate, and butyrate, and protein material to valerate, isovalerate and isobutyrate. ∗ C-2 Acetate ∗ C-3 Propionate Saccharolytic (carbohydrate) fermentation SCFA: >90% of SCFA ∗ C-4 Butyrate ∗ C-6 Caproate

∗ iC4 isoButyrate ∗ C-5 Valerate* ∗ iC5 isoValerate Proteolytic (Protein) fermentation SCFA: < 10% of SCFA ∗ iC6 hexanoate

1. What are short chain fatty acids (SCFA)?

Presenter

Presentation Notes

ibutyrate producing amino acids: valine Valerate producing amino acids: hydroxyproline, proline ivalerate producing amino acids: leucine Other SCFAs such as isobutyrate, isovaleric, valerate and caproate acids are in minor amounts in the colon. The branched chain fatty acids (BCFA), isobutyrate and iso-alerate are primarily produced from catabolism of protein particularly from branched amino acids fermentation. An increase of BCFA tends to be observed only when carbohydrate is limited . Short and medium-chain fatty acids are taken up directly to the portal vein during lipid digestion. Long-chain fatty acids are packed into chylomicrons and enter lymphatic capillaries and enter the blood.

An overview of the relationship between transit of food through the human gastrointestinal tract and the digestion of nutrients in the small intestine and

fermentation in the cecum and colon.

Topping D L , Clifton P M Physiol Rev 2001;81:1031-1064

Presenter

Presentation Notes

An overview of the relationship between transit of food through the human gastrointestinal tract and the digestion of nutrients in the small intestine and fermentation in the cecum and colon. Foods are rendered digestible (comminuted) by processing (milling, cooking) and by mastication in the mouth. Digestion is also enhanced by wetting and macerating in the stomach. In the small intestine, digestion occurs through the action of intrinsic enzymes, and nutrients are absorbed. Food components and endogenous secretions not absorbed in that viscus pass through the ileocecal valve and are fermented. Fermentation is high in the proximal large bowel as is the SCFA production. Absorption of SCFA and of water and minerals (including calcium) is high in this viscus. On passage of the fecal stream, fermentation declines through substrate depletion, and SCFA values fall. The distal large colon and rectum are the regions of the large bowel with the most limited supply of SCFA and are the site of most pathology. Bacteria and unfermented components of low fermentability are voided in the feces. Upon progression to more distal parts of the colon, carbohydrates get depleted, pH increases and protein fermentation becomes more efficient.

1. What do SCFAs do?

∗ More than 95% of SCFA are produced and absorbed within the colon.

∗ SCFA contribute to normal large bowel

function and prevent pathology through their actions in the lumen and on the colonic musculature and vasculature, and through their metabolism by colonocytes.

Topping, D., Clifton, P. Physiol Rev July 1, 2001 vol. 81 no. 3 1031-1064

Presenter

Presentation Notes

SCFA production and absorption are closely related to the nourishment of the colonic mucosa. Less than 5% of bacterially derived SCFA appear in feces due to colonic uptake. Fermentation predominates in the proximal colon and SCFA transported to distal regions by the fecal stream. SCFA levels decline along the distance of the large bowel. The distal colon is the site of greatest organic disease, so the delivery of butyrate to this viscus may be especially important

Acetate Butyrate Propionate

Immune system Immune system Immune system

Carcinogenesis Carcinogenesis Carcinogenesis

Colonic function Colonic function Colonic function

Adipogenesis Satiety Satiety

Barrier function Neurological effects

Visceral perception Cholesterol metabolism

Insulin sensitivity

Oxidative stress

Journal of AOAC International Vol. 95, No. 1, 2012

Presenter

Presentation Notes

Adipogenesis is the process of pre-adipocytes becoming adipocytes. Adipogenesis has been one of the most intensively studied model of cellular differentiation.

Butyrate has been shown to:

Neurogastroenterol Motil (2011) 23, 975–979

∗ Acts as a signal metabolite affecting epithelial cell proliferation, apoptosis, and differentiation.

∗ Affects several inflammatory parameters such as cytokines and myeloperoxidase activity, thus increasing antioxidant capacity.

∗ Provides barrier function: stimulates intestinal mucus production, mucosal repair, and decreases colonic epithelial permeability.

∗ Enhances the growth of lactobacilli and Bifidobacter sp. ∗ Increases mucosal blood flow. ∗ Increases in vitro crypt proliferation. ∗ Clinically can reduce inflammation and diarrhea. ∗ Possible protection against colonic carcinogenesis. ∗ Increases glutathione production.

Acetate has been shown to:

∗ Decreases lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNFα) release from human neutrophils .

∗ Inhibits NF-κB reporter activity in human colon carcinoma cells. ∗ Intravenous administration increases peripheral blood antibody. ∗ Production of natural killer cell activity in cancer patients. ∗ Stimulates proliferation of normal crypt cells. ∗ Enhances ideal motility and increases colonic blood flow. ∗ May have a role in adipogenesis.


Presenter

Presentation Notes

suggests passive diffusion as a likely mechanism of absorption. Furthermore, fecal acetate may reflect absorption, rather than production of colonic acetate.

• Inhibits proinflammatory eicosanoids, nuclear factor-κB, adhesion molecules, LPS-stimulated TNF-α

• Regulates and inhibits proliferation of activated lymphocytes • Growth arrest and differentiation of human colon cancer cells • Induces colorectal cancer apoptosis • Lowers blood glucose and alters lipid metabolism in healthy human

subjects • Increases satiety - Increases production of leptin • Upregulates peroxisome proliferator activated receptor (PPAR)-

gamma • Activates G protein-coupled receptor and inhibits lipolysis • Intraventricular infusions can impair social behavior and cause brain

abnormalities in rats, similar to those detected in human autism.

Propionate has been shown to:


∗ Acetate has been shown to increase cholesterol synthesis. ∗ Propionate has been shown to inhibit cholesterol synthesis. ∗ Treatments that can decrease the acetate/propionate ratio

have been proposed as a way to reduce serum lipids.

Other clinical uses of SCFA: acetate/propionate ratio

J Clin Gastroenterol. 2006 Mar;40(3):235-43.

Presenter

Presentation Notes

Under normal lipidemic conditions, the liver is the most important site of cholesterol biosynthesis, followed by the intestine. Biosynthesis in the liver and intestine account for about 15% and 10%, respectively, of the total amount of cholesterol biosynthesis each day[95,96]. In hypercholesterolemia, when cholesterol biosynthesis is suppressed in most organs by fasting, the intestine becomes the major site of cholesterol biosynthesis, and its contribution can increase up to 50%. Importantly, recent evidence shows that the global effect of butyrate is to downregulate the expression of nine key genes involved in intestinal cholesterol biosynthesis, potentially inhibiting this pathway[97]. Acetate and propionate have been proposed to have opposing effects in hyperlipidemia, a risk factor for coronary heart disease. Subjects given rectal infusions of acetate and propionate in equivalent ratios showed a dose-dependent increase in serum total cholesterol and TG levels, providing indirect evidence that SCFA are utilized for lipid synthesis

Valerate is0butyrate isovalerate

inhibitory effects on cytokine release

strong pungent cheesy or sweaty smell

increase of glutathione (GSH)

proposed that it is the anticonvulsant agent in valerian

induce histone hyperacetylation

major component of the cause of unpleasant foot odor

inhibitory effects on cytokine release

excellent substrate for colonic oxidation, similar to butyrate

Journal of AOAC International Vol. 95, No. 1, 2012

Presenter

Presentation Notes

Isobutyric acid is an isomer of n-butyric acid; they have the same chemical formula C4H8 O2 but a different structure. isovaleric acid, is a natural fatty acid found in a wide variety of plants and essential oils.

Protein Breakdown

∗ Proteins (from foods , albumin, blood, muscle, secretions) must be broken down to peptides and amino acids before bacteria can metabolize them.

∗ Proteins get broken down by bacterial proteases

and peptidases, and pancreatic endopeptidases. ∗ The end product of the breakdown is SCFA, BCFA

and organic acids.

The breakdown of proteins and peptides by colonic microorganisms.

Presenter

Presentation Notes

Compared to carbohydrate digestion in the large gut, the breakdown of proteins and peptides by colonic microorganisms, as well as the ecological and physiologic significance of these substances as carbon, nitrogen, and energy sources, has been largely ignored by the research community. This is somewhat surprising because the deleterious effects of putrefaction in the colon were recognized more than a century ago as being a significant cause of morbidity. Among others, Metchnikoff (127, 128) and Arbuthnot Lane (129) realized that toxic substances or “poisons” formed by intestinal bacteria were associated with autointoxication phenomena, and that fetid breath, depression, sleeplessness, vomiting, severe headaches, increased body temperature, skin diseases, and other extracolonic physiological manifestations were all affected by bacteria colonizing the large bowel.

Metabolism of N-containing substrates in the large gut, and the physiologic significance of the end products.

What affects production of SCFAs? Fecal pH Diet BMI Predominant bacteria Location/Environment Immune Inflammation Race Gender Transit time

Concentration (mmol g dry wt bacteria)

pH 6.8 pH 5.5

Free amino acids

Acetate 10.6 11.7

Propionate 2.8 3.2

Butyrate 1.8 3.2

Valerate 1.9 0.9

ibutyrate 0.5 0.5

ivalerate 2.6 0.9

Total 20.5 20.4

SCFA grown in mixed cultures of intestinal bacteria from amino acids, with a change in pH value.

pH

Presenter

Presentation Notes

Protein degradation accounts for the majority of ammonia occuring in the large intestine while also contributing to SCFA. Ammonia excretion doubled when dietary protein intake went from 63 to 136 grams of protein per day. A pH of less than 5.5 indicates an acidic sample.[Starch intake alone was negatively associated with faecal pH. The increase of fecal |pH-6.6| was significantly associated with the increased mortality. Liver cirrhosis may be accompanied by an imbalance of intestinal bacteria flora. Probiotic supplementation in cirrhosis patients has been found to reduce the level of fecal acidity (pH) and fecal and blood ammonia, which are beneficial changes. relative abundance of lactobacilli in feces of men and animals on vegetarian diets.

High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health.

M (mmol/L) - -> Total SCFA

acetate propionate butyrate valerate isovalerate isobutyrate

maintenance 108.3 61.97 21.10 16.93 2.07 1.14 1.60

high-protein /moderate-carbohydrate (HPMC)

100.6 55.79 17.41 14.83 2.49 1.85 2.28

high-protein /low-carbohydrate (HPLC)

73.59 39.61 14.71 8.54 1.90 1.62 2.01

P <0.001 <0.001 <0.001 <0.001 <0.083 <0.001 <0.002

Short-chain fatty acids (SCFAs) detected in feces of 17 volunteers given 3 different diets.

Am J Clin Nutr May 2011 vol. 93 no. 5 1062-1072

Diet

Presenter

Presentation Notes

↵1 M, maintenance diet; HPLC, high-protein and low-carbohydrate weight-loss diet; HPMC, high-protein and moderate-carbohydrate weight-loss diet; SED, SE of difference. From ANOVA with volunteer as the random effect and diet as the fixed effect (32 residual df). Within a column, significantly different values do not share the same superscript letter.

0

20

40

60

80

100

120

Maintance HPMC HPLC

*

**= <0.001; *= 0.001; ^=.01

^

Am J Clin Nutr May 2011 vol. 93 no. 5 1062-1072

Level of SCFA in three diet groups

Presenter

Presentation Notes

*

0 20 40 60 80 100

acetate

propionate

butyrate

valerate

isobutyrate

isovalerate

Saccharolytic fermentation

Proteolytic fermentation

HPLC HPMC Maintanance

Am J Clin Nutr May 2011 vol. 93 no. 5 1062-1072 **= <0.001; *= 0.001; ^=.01

**

**

*

*

^

Percent

Percent SCFA for three diet groups

Diet/supplements Effects on SCFAs or their derivatives in inflammatory conditions

Diet with resistant starch (1.53 kg/10 kg of diet)

Improvement of symptoms; epithelial cell proliferation; regeneration of laminin; growth of intestinal bacteria

Diet supplemented with cellobiose (9%)

Reduction of weight loss; diminished tissue edema; attenuation of inflammatory cytokine concentrations

Fiber supplementation (5%)

Reduction in MPO and NO synthase activities; restoration of colonic glutathione levels; diminished TNF- concentrations

Oral butyrate (10 mg/kg)

Improvement of mucosa lesion and attenuation of the inflammatory profile of intestinal mucosa and local lymph nodes in a model of DSS-induced colitis.

Nutrients 2011, 3

Factors affecting protein fermentation

The amount of protein entering the colon depends on the amount of protein and the digestibility of the protein eaten.

∗ Decreased digestibility = increased protein fermentation. ∗ Digestibility of proteins from animal sources exceeds 90%; plant proteins

range from 70–90%. ∗ On a normal mixed diet, the amount of protein has a stronger effect on

the amount reaching the colon.

Mol. Nutr. Food Res. 2012, 56, 184–196; November 1, 2010 vol. 299 no. 5 G1030-G1037

Presenter

Presentation Notes

Dairy proteins, whey and casein, appear to be slightly more digestible than meat proteins. meat intake increases fermentation of proteins0 In western diets, on average 15–20% of energy intake is derived from protein intake 11. The amount of protein entering the colon depends on the protein content of the ingested food and protein digestibility. Digestibility of proteins from animal sources (dairy and animal proteins) exceeds 90% and is generally higher than the digestibility of plant proteins (70–90%). Dairy proteins, whey and casein, appear to be slightly more digestible than meat proteins on a normal mixed diet, it is the amount of protein in the diet rather than its source that determines the amount reaching the colon

Carbohydrate Gap

Topping D L , Clifton P M Physiol Rev 2001;81:1031-1064: http://physrev.physiology.org/content/81/3/1031.full

o Fiber is comprised principally of polysaccharides and non-starch polysaccharide (NSP). NSP resist digestion by intrinsic human intestinal digestive enzymes completely, their intakes do not account for calculated human SCFA production (the “carbohydrate gap”).

o Some of the deficit may be filled by oligosaccharides (OS), but starch and products of small intestinal starch digestion are thought to contribute the most. This fraction is termed resistant starch (RS).

o A particular problem is that assay procedures are well-established for fiber and/or NSP but not for RS. This means that dietary intakes can be calculated for the former but not the latter, and direct comparison may be difficult. Thus health authorities have been able to make dietary recommendations for fiber but not yet for RS.

Presenter

Presentation Notes

Thus, in a highly digestible food such as white bread, only 2.8% of available carbohydrate (i.e., starch) appeared in the effluent compared with 13.8% with lentils and 22.6% with high amylose bread. Total starch and resistant starch were increased by three- and sixfold with a simulated Chinese diet compared with a simulated Australian diet (211). This did not lead to putatively beneficial fecal outcomes, but the converse. Fecal mass (86 vs. 141 g/day) and SCFA concentrations were lower (Table 7), and fecal ammonia and phenols were higher on the Chinese diet (211). This study needs to be compared with that of Takahashi et al. (289), which showed that when Japanese subjects ate a similar high-starch diet, fecal SCFA were higher than on a self-selected diet (Table 7). The difference may reflect the relatively short duration of such interventions which last for 3–4 wk, which may be insufficient time for microbial adaptation. Individuals in affluent westernized countries may consume up to 28 g NSP/day

Percentage of carbohydrate loss in relation to GI [adapted from Jenkins et al.]

Wong J M W , Jenkins D J A J. Nutr. 2007;137:2539S-2546S; http://lpi.oregonstate.edu/infocenter/phytochemicals/fiber/ http://lpi.oregonstate.edu/infocenter/phytochemicals/fiber/

Presenter

Presentation Notes

Percentage of carbohydrate loss in relation to GI [adapted from Jenkins et al. (6)].

http://lpi.oregonstate.edu/infocenter/phytochemicals/fiber/

0

20

40

60

80

100

120

BMI 18-24.9 BMI 25-30 BMI 30+ *

Mean SCFA (mmol/l)

BMI

Obesity (2009) 18, 190–195.

Percent SCFA for three BMI levels

* *

Presenter

Presentation Notes

Our results are in line with previous reports suggesting that SCFA metabolism might play a considerable role in obesity.

Percent of total SCFA

Obesity (2009) 18, 190–195.

0 20 40 60 80

acetate

butyrate

propionate

valerate

isobutyrate

isovalerate

>30

25-30

18-24.5

Percent SCFA for three BMI levels

Presenter

Presentation Notes

Below are the mean percentages of SCFAs for three different BMI levels. While the levels were statistically significantly it would hard to say clinically what they mean.

Predominant Bacteria

Predominant bacteria, or normal indigenous microflora, have co-evolved with their host, and play a major role in health. They provide:

∗ Colonization resistance against potentially pathogenic organisms ∗ Aid in digestion and absorption ∗ Produce vitamins and SCFAs ∗ Stimulate the GI immune system ∗ Are able to activate innate and adaptive immunity

Presenter

Presentation Notes

The immune system has developed specialized regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous food or air-born antigens and predominate bacteria to avoid unlimited immune response.

SCFA Production Acetate Propionate Butyrate Lactate

Bacteroides x x X (D)

Bifidobacteria x X (L)

Lactobacilli x X (D/L)

Clostridia x x x X (L)

Faecalibacteria x X (D)

Fusobacteria x x

Prevotella X

GI tract with bacteria populations shown by region

Anaerobes dominate the gut.

Bacterial Phylumm Bacteroidetes

∗ Bacteroides spp. ∗ Prevotella spp.

Firmicutes ∗ Clostridia spp. ∗ Mycoplasma spp. ∗ Lactobacillus spp.

Proteobacteria ∗ Escherichia coli.

Fusobacteria ∗ Fusobacteria spp.

Actinobacteria ∗ Bifidobacter spp. ∗ Streptomyces spp.

Predominant Bacteria based on diet

0 10 20 30 40

Bacteroides

Lachnospiraceace

Roseburia

F. prausnitzil

HPLC HPMC Maintanance

**

*

** p= <.001; * p< .05 Am J Clin Nutr May 2011 vol. 93 no. 5 1062-1072

Bifidobacter content in RATS fed varying diets

CT – Control diet ; HF – High fat diet

HF-Cell – High fat with non-fermentable fiber

HF-OFS – High fat with fermentable fiber

aberrant crypts per/cm2

J Nutr. 1999 Jul;129(7 Suppl):1483S-7S

Dietary levels of oligofructose and Bifidobacter sp. resulted in a decrease in aberrant crypts in RATS

OF – Oligofructose (inulin)

SBO – Soybean oligosaccharide;

WBO – Wheat bran oligosaccharide

Presenter

Presentation Notes

Of OF, SBO and WBO, only SBO reduced the colonic mucosa proliferation compared with the control. These results suggest that the combination of bifidobacteria and oligofructose reduces colon cancer risk in carcinogen-treated rats, but the effect of other oligosaccharides is uncertain. J. Nutr. 129: 1483S–1487S, 1999J Nutr. 1999 Jul;129(7 Suppl):1483S-7S. Links The effect of symbiotics on colon carcinogenesis in rats. Gallaher DD, Khil J. A number of studies in animal models of colon cancer have suggested that either dietary oligofructose (or inulin) or consumption of bifidobacteria could reduce the incidence of colon cancer. Figure 4. Effect of bifidobacteria combined with three different oligosaccharides on the number of aberrant crypts. OF, oligofructose; SBO, soybean oligosaccharide; WBO, wheat bran oligosaccharide. Values are shown as box plots because the data were not normally distributed. The center line of each box represents the median, the top and bottom of the boxes represent the 25th and 75th percentile of the data, respectively, and the top and bottom of the error bars represent the 5th and 95th percentile of the data, respectively. *Significantly different from the control group by t test (P < 0.05).

PNAS August 17, 2010 vol. 107 no. 33 14691-14696

Comparative study in children from Europe (EU) and rural Africa (BF)


SCFA-producing bacteria could help to prevent establishment of some potentially pathogenic intestinal bacteria. Quantification of SCFAs in fecal samples from BF and EU populations by SPME-GC-MS.


51.17%

13.64%

33.92%

1.20%

69.54%

8.30%

20.10%

1.70%

0% 20% 40% 60% 80% 100%

Acetate

Butyrate

Propionate

Valerate

EU BF


40.2

31.2

148.6

14.2

66.7

73.9

290

8.4

0 50 100 150 200 250 300

protein

fat

carbohydrate*

fiber

EU

BF

Grams of macronutrients



Presenter

Presentation Notes

Total kcal996 BF1512 EU Whole grains are concentrated sources of dietary fiber, resistant starch, and oligosaccharides, as well as carbohydrates that escape digestion in the small intestine and are fermented in the gut, producing short-chain fatty acids (SCFAs). Xylanibacter, Prevotella, Butyrivibrio, and Treponema are exclusive to the BF children (Fig. S2) and indicate the presence of a bacterial community using xylane, xylose, and carboxymethylcellulose to produce high levels of SCFAs (18) whose protective role against gut inflammation has been well proven (19). These bacteria can ferment both xylan and cellulose through carbohydrate-active enzymes such as xylanase, carboxymethylcellulase, and endoglucanase

Frequency of genes relayed to butyrate, acetate and propionate production in the fecal metagenome of 27 subjects.

Nature, 2012; http://www.nature.com/nature/journal/vnfv/ncurrent/extref/nature11319-s1.pdf

Environment

Presenter

Presentation Notes

Frequency of genes relayed to butyrate, acetate and propionate production in the fecal metagenome of 27 subjects. Comparison of A) gene counts and B) average sequencing coverage, for enzymes involved in butyrate, acetate and propionate production. Gene count values were normalised for 4.79 x 109 of sequenced bases per subject, and coverage values were normalised for the average coverage in each metagenome. BCoAt: Butyryl-CoA transferase/Acetyl-CoA hydrolase; ACS: Acetate-formyltetrahydrofolate synthetase/Formate-tetrahydrofolate ligase; PCoAt: Propionyl-CoA:succinate-CoA transferase/Propionate CoA-transferase.

http://www.nature.com/nature/journal/vnfv/ncurrent/extref/nature11319-s1.pdf

Presenter

Presentation Notes

Figure 7 | Predicted gene counts and assembly statistics for the faecal metagenome of 27 selected subjects. The graphs show total gene counts and sequencing assembly N50 values for shotgun sequence data of the faecal metagenome for 27 subjects of indicated residence location. http://www.nature.com/nature/journal/vnfv/ncurrent/extref/nature11319-s1.pdf

J. Pediatr Gastroenterol Nutr, Vol. 18, No. 2, 1994.

Fecal Short Chain Fatty Acids in Children with Inflammatory Bowel Disease

White bars= controls; black = severe UC; grey= inactive/mild UC

Immune Reactions

Inflammation

0 50 100 150 200 250

acetate

butyrate

propionate

isobutyratelactate

IBS Healthy

(*P<0.05).

*

*

Open Biochem J. 2010; 4: 53–58.

Amount of SCFAs in each population

Colonic contents of the primary SCFA in African Americans, Caucasian Americans, and Native Africans.

O'Keefe S J D et al. J. Nutr. 2009;139:2044-2048

Race

Presenter

Presentation Notes

Colonic evacuant contents of the primary SCFA in African Americans, Caucasian Americans, and Native Africans. Values are means ± SE, n = 17 or 18. Asterisks indicate different from Native Africans: *P < 0.05, **P < 0.005. In conclusion, the results support our hypothesis that the microbiota mediates the affect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

Case Study

Patient symptoms ∗ belching ∗ flatulence ∗ bloating ∗ abdominal pain ∗ diarrhea ∗ fatigue

∗ Diet history - vegetarian diet - tries to avoid dairy ∗ Symptom questionnaire- meets criteria for IBS ∗ Symptom history ∗ Laboratory assessment of GI function ∗ Do a stool test ∗ Look to see if the patient has vitamin D, B12, or iron

∗ Consider getting these or other fat soluble vitamins ∗ Also consider amino acids

Collect

Resident Micro-biota

Short Chain Fatty Acids

Acetate / Propionate = 48/4.5= 10.66 Average A/P ratio = 3.075 Total cholesterol: 209 HLD: 41 and Lp(a): 75

Percent Short Chain Fatty Acids

12.66

87.27

7.63

92.37

4.76

91.77

7.3

92.7

0 20 40 60 80 100

Proteolytic fermentation

Saccharolytic fermentation

Percent

Case HPLC Maintenance Normal BMI

(Isobutyrate + isovalerate + valerate)

Evaluation of Digestive Markers

Thermogram Results

Treatment options

∗ Use of butyrate ∗ Butyrate functions as the major energy source for colonocytes and modulates

several cellular processes

∗ Changes in dietary habits ∗ Increasing fiber intake of soluble fibers (fermentable) is more effective than

insoluble (non-fermentable), which can increase SCFAs (butyrate). ∗ Decrease total protein intake, or shift to more plant protein. This will result in a

shift from proteolytic to saccharolytic fermentation. ∗ Exclude dairy and casein

∗ Use of prebiotics ∗ Specifically inulin

∗ Product Klaire labs Biotagen ∗ Increase diet sources: artichoke hearts, banana, agave, garlic, onion, wild yam, chicory

Presenter

Presentation Notes

The amount of these SCFAs produced in the colon depends on the site of fermentation, the diet composition, gut transit time and the composition of the colonic microbial flora. Soluble fibers (fermentable) are more effective than insoluble (non-fermentable) in alleviating global symptoms and relieving constipation, although fiber in general has only a marginal benefit in treatment of overall IBS symptoms.

Assessing Gut Issues: Short Chain Fatty Acids

Elizabeth Redmond, PhD, MMSc, RD [email protected] Metametrix Laboratory, Georgia Chair-Elect Dietitians in Integrative and Functional Medicine DPG

mailto:[email protected]

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Assessing Gut Issues: Short Chain Fatty Acids...Predominant gut bacteria ferment dietary fiber and their monosaccharide components to acetate, propionate, and butyrate, and protein