Advances

in functional gastroenterology:
management of SIBO, endotoxemia and
common gastrointestinal disorders

Benjamin I. Brown, ND
 Disclosures and Affiliations
Benjamin I. Brown, ND
Editor, Journal of Orthomolecular Medicine
Contributing Editor, Integrative Health and Applied Nutrition
Board and Lecturer, BCNH College of Nutrition and Health
Director of Clinical Education, Pure Encapsulations UK
Author, The Digestive Health Solution
Host, Positive Health Podcast
E: ben@timeforwellness.org
W: timeforwellness.org
@BenBrownND
Chronic and debilitating
ü People had suffered from IBS for
an average of 16.6 years
ü 50% of people with IBS had had
symptoms for more than ten years
ü 57% experienced symptoms daily

Eur J Gastroenterol Hepatol. 2001 Nov;13(11):1327-32

 SYMPTOMS

VARIOUS Significant shortcomings in IBS

diagnosis and treatment may arise
UNDERLYING CAUSES from IBS being an ‘umbrella’
diagnosis that clusters several
underlying identifiable and treatable
causes for the same symptom
presentation into one classification.
Varied diagnosis

“Abdominal symptoms meeting Rome III criteria for IBS

were present in 3553 records (the population), which were
subjected to further analysis. Abnormal biomarker results
(the outcomes) occurred in 94% of cases...”

Frontline Gastroenterol. 2016 Oct;7(4):275-282.

Varied mechanisms

Nat Rev Dis Primers. 2016 Mar 24;2:16014.

Disease delusion

“The temptation to develop a catalogue of functional

disorders to encompass all unexplained gastrointestinal
symptoms has led to the illusion that an unexplained
symptom is itself a discrete ‘disease’.”

Clin Med (Lond). 2009 Apr;9(2):131-5.

Defining ‘function’

“The functional medicine model for health care is concerned

less with what we call the dysfunction or disease, and more
about the dynamic processes that resulted in the person's
dysfunction. The previous concept of functional somatic
syndromes as psychosomatic in origin has now been
replaced with a new concept of function that is rooted in
the emerging 21st-century understanding of systems
network-enabled biology.”

Integr Med (Encinitas). 2017 Feb;16(1):22-25.

Obtaining a better understanding of
each patients pathophysiology with
clinical and molecular assessments
could therefore help improve diagnosis
and target different therapies to
individuals most likely to benefit.
Underlying causes of
Irritable Bowel Symptoms • Stress
• Circadian disruption
• Physical inactivity

Lifestyle &
environme-
ntal factors
• Exocrine pancreatic insufficiency
• Low-grade inflammation
• Intestinal permeability
• Bile acid malabsorption • Carbohydrate intolerance
• Chronic constipation • Food hypersensitivity
• Dysbiosis • Non-celiac gluten sensitivity
• Small intestinal bacterial overgrowth Irritable • Nickel-related intestinal mucositis
• Parasitic infection or overgrowth Bowel • Vitamin D deficiency
Symptoms

Functional Nutritional
imbalances factors

Brown, BI. Does Irritable Bowel Syndrome Exist? [submitted for publication]
Small intestinal
bacterial
overgrowth
SIBO

Small intestinal bacterial overgrowth (SIBO) is defined as an

abnormally high number and/ or type of bacteria in the
small bowel. This overgrowth is typically colonic gram-
negative aerobes and anaerobic species that ferment
carbohydrate and play a role in the development of
symptoms characteristic of SIBO including bloating,
flatulence, abdominal discomfort and changes in stool form.

Ther Adv Chronic Dis. 2013 Sep;4(5):223-31.

Distribution of bacterial populations

Gastroenterol Clin North Am. 2017 Mar;46(1):103-120.

Small intestinal bacterial overgrowth

JAMA. 2004 Aug 18;292(7):852-8.

Major gut defense mechanisms preventing SIBO

Gastroenterol Clin North Am. 2017 Mar;46(1):103-120.

 Risk factors for the development of SIBO
Risk factors for the development of SIBO include anatomical changes,
alterations in motility, reduced pH, and immunological factors:
ü Examples of anatomical changes include, small-bowel obstruction, small-
bowel diverticula, and postsurgical anatomical alterations.
ü Changes in motility may be primary (i.e. gastroparesis), or secondary to
conditions such as Parkinson disease, hypothyroidism or diabetes mellitus.
ü Alterations in pH are linked to hypochlorhydria, proton pump inhibitor use,
and advanced age.
ü And immunological factors include IgA deficiency, combined variable
immunodeficiency, and human immunodeficiency virus.

Clin Proc. 2016 Dec;91(12):1828-1833.

 Symptom overlap with irritable bowel syndrome
SIBO is also associated with chronic diarrhea, steatorrhea, and pale stool due
to dilution of bile pigment in a large volume of stool

SIBO can mimic symptoms of irritable bowel syndrome (IBS) and case-
control studies have generally found a higher prevalence of SIBO among
patients with IBS (19% to 37%) comparted to healthy controls (0% to 12%).

Treating SIBO may relieve symptoms consistent with IBS.

 Intestinal & extra-intestinal disease associations
Several intestinal as well as extra-intestinal disease associations with SIBO
have been described including:

ü inflammatory bowel diseases ü restless legs syndrome

ü gastroparesis
ü chronic diarrhea
ü treatment refractory celiac disease
ü chronic pancreatitis
ü erosive esophagitis
ü hepatic encephalopathy
ü rosacea
ü chronic urticaria
ü fibromyalgia
ü rheumatoid arthritis
ü hypothyroidism
ü obesity
ü subclinical atherosclerosis
ü deep vein thrombosis,
ü Parkinson's disease
ü multiple sclerosis
 Cause or association?
In some cases, for example rosacea and restless legs
syndrome, treating SIBO has been shown to result
in clinical improvement of extra-intestinal
symptoms, but a causal role between SIBO and
associated illnesses often remains speculative and
the development SIBO could be secondary to
illnesses that alter gastrointestinal motility, as in
hypothyroidism and Parkinson’s disease.
When to treat?

If clinical features suggest SIBO, the clinician has two

options: test and treat, or treat empirically

Curr Opin Gastroenterol. 2014 Mar;30(2):141-6

 Functional medicine-based framework
Management of SIBO is typically based on antibiotic therapy, of which a
variety have been used and result in an overall rate of breath test normalization
of 50% compared with 10% for placebo. Alternatives to antibiotics include
probiotics and herbal therapy.

A functional medicine-based approach may help identify modifiable

physiological factors that contribute to the development of SIBO, as well as
aid in the development personalized dietary, nutritional and herbal therapies
that target dysbiosis.

Possible consequences of SIBO, such as malabsorption and intestinal

permeability, should also be considered.
 Functional Considerations

Reduced motility

Intestinal
inflammation SIBO Hypochlorhydria

Pancreatic exocrine
insufficiency
 The migrating motor complex
Between meals and during fasting the stomach and small intestine normally
has a periodic migrating band of contractions that are known as the migrating
motor complex (MMC).
ü The MMC is considered the “intestinal housekeeper” as it protects against
SIBO, most likely because the contractions clear out the luminal content
toward the lower intestines.
ü Disturbed MMC activity has been implicated as an important cause of
SIBO.
ü And lower MMC frequency has been found in people with the dual clinical
presentation of IBS and SIBO.
Methanogens

A dysbiotic overabundance of methane-producing

bacteria, as determined via breath test, is associated with
slow transit time that improves after antibiotic therapy.

J Neurogastroenterol Motil. 2011 Apr;17(2):185-8.

Gas slows transit

Methane itself may slow gut transit by altering the

contractile pattern of the gut, reducing normal peristaltic
activity and inducing a more spastic contractile pattern.

Curr Gastroenterol Rep. 2013 Dec;15(12):356.

Probiotics

In people with constipation predominant irritable bowel

syndrome (IBS), Lactobacillus reuteri DSM 17938 (100
million CFU) 30-minutes after eating twice daily for 4-
weeks significantly decreased methane gas production,
as determined by a lactulose breath test. The reduction
in methane production was associated with a significant
increase in bowel movements and regularity.

Eur Rev Med Pharmacol Sci. 2017

Apr;21(7):1702-1708.
Stressed gut

Psychological stress has been shown to reduce MMC

activity and motility, suggesting mind-body interventions
could be a useful consideration.

Neurogastroenterol Motil. 2004

Dec;16(6):737-44.
Prokinetic therapy

“In this study, we demonstrate for the first time that

prokinetic therapy appears to maintain remission of
symptom recurrence in IBS patients after treatments
based on a bacterial overgrowth hypothesis.”

Gastroenterol Hepatol (N Y). 2009

Jun;5(6):435-42.
Ginger

“This study was undertaken to study

the prokinetic action of ginger and its possible
mechanism of action. Prokinetic activity of ginger extract
was confirmed in an in vivo test when it enhanced the
intestinal travel of charcoal meal in mice.”

Dig Dis Sci. 2005 Oct;50(10):1889-97.

Gastric motility

Ginger markedly and stimulated antral

contractions

Eur J Gastroenterol Hepatol. 2008

May;20(5):436-40.
Gastric emptying

Gastric emptying was more rapid after

ginger than with placebo [T50: 12.3 (8.5-
17.0) min vs 16.1 (8.3-22.6) min, P ≤ 0.05)].

World J Gastroenterol. 2011 Jan 7;17(1):105-10

 A role for extending time between eating?
Fasting between meals, avoiding snacking, and
fasting 12 hours overnight has been postulated to
improve MMC function and reduce SIBO.

Today’s Dietitian. 2012 Vol. 14 No. 12 P. 16

 Functional Considerations

Reduced motility

Intestinal
inflammation SIBO Hypochlorhydria

Pancreatic exocrine
insufficiency
 Hypochlorhydria can result in SIBO
Gastric acid suppresses the growth of bacteria in
the small intestine. Accordingly, hypochlorhydria
due to chronic atrophic gastritis, helicobacter
pylori infection, proton pump inhibitor use, or
related to older age may cause SIBO.
 Hypochlorhydria
ü Hypochlorhydria symptoms may include; feeling
unusually full after small or moderate-sized meals,
belching, flatulence, morning diarrhea, diarrhea after
heavy meals, constipation, heartburn, indigestion, and
a sensation that food sits for a long time in the stomach

ü Chronic hypochlorhydria has also been reported to

occur after gastroenteritis

ü 1–3 capsules of Betaine HCl per meal (520 mg per

capsule) may be effective for relieving gastrointestinal
symptoms

Hypochlorhydria. In, Gaby, AR. Nutritional Medicine, 2011.

 Re-acidification
Supplementation with a single dose of betaine HCl has been shown to re-acidify the
stomach in volunteers with hypochlorydia. In this study a single dose of 1500 mg
decreased gastric pH on average from pH 5 to 1, with a gastric pH <3 achieved on
average for 73 minutes.

Mol Pharm. 2013 Nov 4;10(11):4032-7.

 Functional Considerations

Reduced motility

Intestinal
inflammation SIBO Hypochlorhydria

Pancreatic exocrine
insufficiency
 Pancreatic exocrine insufficiency
There is a higher risk for SIBO in patients with chronic pancreatitis, and
exocrine pancreatic insufficiency is present in a subgroup of with IBS.

Several factors related to pancreatic exocrine insufficiency may predispose to

SIBO, including fat malabsorption, absence of anti-bacterial effect of
proteolytic enzymes, and alterations in motility.

Pancreatic enzyme replacement therapy is a useful treatment for both chronic

pancreatitis and IBS-symptoms related to exocrine pancreatic insufficiency,
but effects on bacterial overgrowth have not been explored.
 Functional Considerations

Reduced motility

Intestinal
inflammation SIBO Hypochlorhydria

Pancreatic exocrine
insufficiency
 Intestinal inflammation
There may be a bi-directional relationship between SIBO and intestinal
inflammation.

On one hand, SIBO has been suggested to play a causative role in intestinal
inflammation in patients with irritable bowel syndrome and inflammatory
bowel disease.

While, conversely, the presence of inflammation can directly cause expansion

of pathogenic bacteria and severe dysbiosis.
Inflammation creates dysbiosis

EMBO Rep. 2013 Apr;14(4):319-27.

 Boswellia serrata extract
Bowsellia extract (250 mg per day,
providing 25% boswellic acids) was
compared to drug therapy with the
antispasmodics hyoscine
butylbromide or papaverine
hydrochloride + A. belladonna over
a 4-week treatment period.

Boswellia extract was as effective

as the medications for symptoms
such as abdominal pain, altered
bowel movements, and cramps but
also resulted in less need for
medical attention and lower
incidence of side effects.

Eur Rev Med Pharmacol Sci. 2017 May;21(9):2249-2254.

 Functional Considerations

Reduced motility

Intestinal
inflammation SIBO Hypochlorhydria

Pancreatic exocrine
insufficiency
Clinical summary

Functional considerations
• Reduced motility
• Hypochlorhydria
• Pancreatic exocrine insufficiency
• Intestinal inflammation
Food-based interventions
• Low-fermentable carbohydrate diet
• Elemental diet
Nutritional and botanical interventions
• Herbal medicine
• Probiotics
Sweet loving

“…small intestine communities are depending on the

capacity for fast import and conversion of relatively
simple carbohydrates and rapid adaptation to the overall
nutrient availability, which contrasts the specialization
towards the efficient degradation of complex
carbohydrates that is seen in colonic microbial
communities.”

ISME J. 2012 Jul;6(7):1415-26.

Low fiber

“Subjects with a positive hydrogen breath test

consumed significantly less fiber, folic acid, and vitamins
B2 and B6 than those without. No difference was
observed in the intake of energy, protein, fat, or
carbohydrates.”

J Am Geriatr Soc. 2003;51:768–773

High sugar

“Obese patients with small intestinal bacterial

overgrowth (SIBO) ingested more carbohydrates (252.75
vs 201 g/day), more refined sugars (104.15 vs 73.32
g/day) and less total and insoluble fibers (9.6 vs 14.65
g/day and 4.7 vs 8.82 g/day, respectively).

Scand J Gastroenterol. 2016 Mar;51(3):277-80.

Low fermentable
diet?
“Theoretically, a diet with low fermentable foods can
decrease the chance of bacterial overgrowth by creating
a less favorable luminal environment for overgrown
bacteria.”

Curr Gastroenterol Rep. 2016 Feb;18(2):8.

SIBO eradication
& FODMAPs
“Small intestinal bacterial overgrowth eradication, as
confirmed by negative lactulose breath test, caused a
significant reduction in lactose, fructose and sorbitol
breath tests positivity (17% vs. 100%, 3% vs. 62%, and
10% vs. 71% respectively: P < 0.0001).”

Aliment Pharmacol Ther. 2005 Jun

1;21(11):1391–5.
Elemental diet

Treatment of people with IBS and SIBO with an

elemental diet for 2-weeks normalized breath tests in
80% of people, and in non-responders a further 1-week
of treatment resulted in a total response rate of 85%. At
1-month follow-up those who normalized their breath
test showed a 66 % improvement in symptoms,
compared to 11.9% in non-responders.

Dig Dis Sci. 2004 Jan;49(1):73-7.

Herbal therapy

Successful treatment of SIBO, as confirmed with a follow-

up breath test, was 46% in the herbal therapy group vs.
34% in those who received rifaximin. People who did not
respond to rifimaxin were offered either a stronger course
of antibiotics or herbal therapy, which were equally
effective at eradicating SIBO (both about a 60% successful
treatment). Adverse events in those receiving herbal
therapy were lower than rifaximin (1 vs. 6).

Glob Adv Health Med. 2014 May;3(3):16-24.

Probiotics

A review and meta-analysis including

22 studies of probiotic therapy for
SIBO found that they were effective
overall for reducing SIBO, decreasing
breath hydrogen concentration, and
relieving abdominal pain.

J Clin Gastroenterol. 2017 Apr;51(4):300-311.

Adjuvant probiotics

The addition of a probiotic resulted in better resolution of

SIBO compared to antibiotic therapy alone (a negative
hydrogen breath test in 93.3% with probiotics vs. 66.7%
without) as well as superior symptomatic improvement.

J Med Res. 2014 Nov;140(5):604-8

Metabolic
Endotoxemia
Auto-intoxication

‘man is constantly standing, as it were, on the brink of a

precipice; he is continually on the threshold of disease.
Every moment of his life he runs the risk of being
overpowered by poison generated within his system’

Bouchard. Lectures on autointoxication in

disease, 1897.
Re-defined
“We found that normal endotoxemia increased or
decreased during the fed or fasted state, respectively, on
a nutritional basis and that a 4-week high-fat diet
chronically increased plasma LPS (endotoxin)
concentration two to three times, a threshold that we
have defined as metabolic endotoxemia.”

Diabetes. 2007 Jul;56(7):1761-72.

 Dysbiosis
Microbiota

Luminal Endotoxin Increased Endotoxin Reserve

Intestinal alkaline
phosphatase
Gap Junction Intestinal permeability

Lactoferrin
Metabolic Endotoxemia

Intracellular
Transport Metabolic Perturbations

Paracellular Disease Development

Transport
Divergence

“Diet-induced, metabolic endotoxemia is emerging as

an important contributory factor to the development of
a wide range of chronic diseases, including
cardiometabolic, autoimmune, psychiatric, and
neurodegenerative illnesses.”

Altern Ther Health Med. 2017 Jul;23(4):42-54.

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
Metabolic endotoxemia

Cani PD, et al. Microbes. 2012 Jul-Aug;3(4):279-88.

Western diet

“Two general changes can be observed consumption of

a high-fat, low-fiber diet. First, pathobionts can expand
during consumption of a high fat diet, and second, the
abundance of protective bacteria, such as producers of
short chain fatty acids, declines.”

Curr Opin Lipidol. 2015 Apr;26(2):73-81.

High-fat diet (HFD) induces pathobiont expansion

Curr Opin Lipidol. 2015 Apr;26(2):73-81.

Nat Rev Immunol. 2003 Feb;3(2):169-76.
Curr Opin Lipidol. 2013 Feb;24(1):78-85.
 Dysbiosis
Microbiota

Luminal Endotoxin Increased Endotoxin

Intestinal alkaline
phosphatase
Gap Junction

Intracellular
Transport

Paracellular
Transport
Alkaline phosphatase

“Intestinal alkaline phosphatase is at the crossroads

between diet, fat absorption, the microbiota, LPS, and
inflammation, factors that have all been implicated as
causal in obesity and metabolic disorders.”

Nutr Rev. 2014 Feb;72(2):82-94.

Intestinal alkaline phosphatase (ALP) is an important
enzyme in lipopolysaccharide (LPS) detoxification

Nutr Clin Pract. 2012 Apr;27(2):215-25.

 Dysbiosis
Microbiota

Luminal Endotoxin Increased Endotoxin

Intestinal alkaline
phosphatase
Gap Junction Intestinal permeability

Intracellular
Transport

Paracellular
Transport
Transcellular and paracellular transport pathways for lipopolysaccharide
(LPS) movement from the enteric lumen into circulation.

Nutr Clin Pract. 2012 Apr;27(2):215-25.

 Dysbiosis
Microbiota

Luminal Endotoxin Increased Endotoxin

Intestinal alkaline
phosphatase
Gap Junction Intestinal permeability

Lactoferrin
Metabolic Endotoxemia

Intracellular
Transport

Paracellular
Transport
Lactoferrin

“Serum endotoxin levels were significantly associated

with circulating LPS binding protein (LBP)
concentration. Circulating LBP concentration could be
a specific marker of metabolic endotoxemia. Endotoxin
levels also were inversely associated with circulating
lactoferrin association.”

J Clin Endocrinol Metab. 2009 Oct;94(10):4036-44

 Dysbiosis
Microbiota

Luminal Endotoxin Increased Endotoxin

Intestinal alkaline
phosphatase
Gap Junction Intestinal permeability

Lactoferrin
Metabolic Endotoxemia

Intracellular
Transport Metabolic Perturbations

Paracellular Disease Development

Transport
Altern Ther Health Med. 2017 Jul;23(4):42-54.
 Disease associations from human studies
• Cardiovascular disease risk • Depression
• Obesity • Schizophrenia
• Metabolic syndrome • Neurodegenerative disease
• Type 2 diabetes • Chronic fatigue syndrome
• Diabetic nephropathy
• Nonalcoholic fatty liver disease
• Inflammatory bowel disease
• Colorectal cancer
• Infertility
• Autism

Altern Ther Health Med. 2017 Jul;23(4):42-54.

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
 Sugar and fat “double hit”
“…acellular flours, sugars, and processed foods produce an inflammatory
microbiota via the upper gastrointestinal tract, with fat able to effect a "double
hit" by increasing systemic absorption of lipopolysaccharide.”

Diabetes Metab Syndr Obes. 2012;5:175-189

Single meal

The unhealthy meal

increased plasma LPS
concentration and
oxidative and
inflammatory stress.

These increases were

totally absent after the
meal rich in fiber and
fruit.

Diabetes Care. 2009 Dec;32(12):2281-7.

Quality - not only quantity - counts

Caesar R, et al. Crosstalk between Gut

Microbiota and Dietary Lipids Aggravates
WAT Inflammation through TLR Signaling.
Cell Metab. 2015 Aug 26
Long-term

The Western-style diet

induced a 71% increase in
plasma levels of
endotoxin activity.

A prudent-style diet
reduced levels by 31%.

Gastroenterology. 2012 May;142(5):1100-1101.e2

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
Prebiotic drink

“Chronic red wine consumption increases

Bifidobacterium and Prevotella amounts, which may
have beneficial effects by leading to lower LPS
concentrations.”

Am J Clin Nutr. 2013 May;97(5):1053-61

Toxic drink

“Our findings indicate that even a single alcohol binge

results in increased serum endotoxin levels likely due
to translocation of gut bacterial products and disturbs
innate immune responses that can contribute to the
deleterious effects of binge drinking.”

PLoS One. 2014 May 14;9(5):e96864

Toxic drink

PLoS One. 2014 May 14;9(5):e96864

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
 Micronutrient deficiencies and endotoxemia
Nutrient Mechanism
Vitamin A Causes dysfunctional epithelial barrier due to role in the expression of
genes related to tight junctions
Magnesium Reduces bifidobacteria and lowers expression of tight junction
proteins occludin and zonulin
Zinc Deficiency disassembles tight junction proteins and sensitizes gut to
toxic insult
Vitamin D Vitamin D receptor (VDR) plays a critical role in
mucosal barrier homeostasis; preserves integrity of junction
complexes and stimulates epithelial renewal
Vitamin C Deficiency-induced endotoxin influx into portal blood from the
gastrointestinal tract

Altern Ther Health Med. 2017 Jul;23(4):42-54.

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
 Nature 518, S9
(26 February 2015)
Pharmacology & Therapeutics 130 (2011) 202–212
Pharmacology & Therapeutics 130 (2011) 202–212
Prebiotics

In women with type 2 diabetes, supplementation with

prebiotics (10 g of oligofructose-enriched inulin daily) for
8-weeks significantly reduced plasma endotoxin (21.95%),
compared to placebo. Furthermore, the prebiotic group
also had significant improvements in glucose control and
reductions in some inflammatory markers.

Nutrition. 2014 Apr;30(4):418-23.

Probiotics

“In healthy adults an exploratory 4-week study of a

probiotic (Lactobacillus reuteri; 20 billion daily) on blood
glucose tolerance found that the probiotic treatment
stabilized serum endotoxin levels and improved glucose-
dependent insulin release compared to placebo.”

Diabetes Care. 2015 Jun 17.

pii: dc142690. [Epub ahead of print]
 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
 Polyphenols shape the microbiome
“…polyphenols are able to kill or inhibit the growth of microorganisms such
as bacteria, fungi, or protozoans. Some dietary polyphenols may have
significant effects on the colonic flora providing a type of prebiotic effect.”

Crit Rev Food Sci Nutr. 2012;52(10):936-48

 Polyphenols or polyphenol rich foods
Experimental research into the effects of specific polyphenols or polyphenol
rich foods in high-fat diet induced metabolic endotoxemia suggests turmeric,
cocoa, tetrahydro iso-alpha acids from hops, and polyphenol-rich cranberry
extract can lower serum endotoxin and improve metabolic markers.

Altern Ther Health Med. 2017 Jul;23(4):42-54.

Pre-meal resveratrol

At 10 minutes prior to a high-fat, high-carbohydrate meal

of 930 kcal, a polyphenol dietary supplement—a
Polygonum cuspidatum extract providing 100 mg of
resveratrol with a grape extract providing 75 mg of total
polyphenols—or a placebo. Whereas the placebo group
had a postprandial rise in plasma endotoxins, with a
median 60% elevation, the supplement group exhibited a
decrease below baseline, a median 28% reduction, as well
as significant reductions in markers of inflammation and
oxidative stress when compared to the placebo.

J Clin Endocrinol Metab. 2011;96(5):1409-1414.

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin
Prebiotics

Glutamine Polyphenols
Prebiotic effects

“Oral supplementation with glutamine (30 g/ day), for a

short time, altered the composition of the gut microbiota
in overweight and obese humans reducing the Firmicutes
to Bacteroidetes ratio, which resembled weight loss
programs already seen in the literature.”

Nutrition. 2015 Jun;31(6):884-9.

Prebiotic effects

In mice fed a western-style diet, glutamine supplementation

for 6-weeks reduced portal endotoxin elevation, reduced
oxidative stress and inflammation, improved fasting glucose,
and reduced liver damage when compared to a western-style
diet without glutamine.

J Nutr. 2015 Aug 5. pii: jn215517.

[Epub ahead of print].
 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin Prebiotics

Glutamine Polyphenols
Toxic buffering

“A decreased production of anti-LPS proteins and

peptides were associated with insulin resistance, obesity,
vascular dysfunction, hepatic dysfunction and dyslipidemia.
A partial lost in the buffering efficiency of LPS could
increase its negative effects on metabolism.”

Av Diabetol. 2009;25:78-85
 Lactoferrin for diet-induced endotoxemia?
ü Lactoferrin is involved in endotoxin buffering and other anti-microbial and
anti-inflammatory effects, and is available as a dairy (whey) derived dietary
supplement.

ü In mice, supplementation with lactoferrin mitigated the effects of a high-

fructose diet on intestinal bacterial overgrowth, intestinal permeability, and
endotoxemia.

ü In men and women with abdominal obesity, supplementation with enteric

coated lactoferrin (300 mg daily) for 8-weeks resulted in a significant decrease
in body weight and visceral fat.

Altern Ther Health Med. 2017 Jul;23(4):42-54.

Colostrum

“…colostrum supplementation (500 mg/ twice daily, 20-

days) decreased previously elevated intestinal permeability
and was able to restore it to a predetermined normal limit
within less than 3 weeks of relatively mild
supplementation. Colostrum supplementation also
decreased zonulin concentration in the gut, but to a lesser
degree than its influence on permeability.”

Nutrients. 2017 Apr 8;9(4)

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin Prebiotics

Glutamine Polyphenols
 Cardiometabolic benefits possibly due to G.I. effects
ü Berberine is an alkaloid present in a number of plants traditionally used to
treat gastrointestinal illnesses; indeed, clinical studies have lent support to its
important antidiarrheal activity.

ü Berberine has undergone extensive clinical investigation for T2DM,

dyslipidemia, and hypertension and has shown well-documented effects in
those metabolic diseases.

ü The intersection of gastrointestinal and cardiometabolic benefits, coupled

with the poor oral bioavailability of berberine, could be explained in part by its
modulatory effects on the gut microbiota and gut-derived endotoxins.

Altern Ther Health Med. 2017 Jul;23(4):42-54.

 Dietary
interventions

Fermented
Alcohol
foods

Micronutrient
Berberine
deficiencies
Nutritional Management of
Metabolic Endotoxemia

Probiotics/
Lactoferrin Prebiotics

Glutamine Polyphenols
Fermented

“ fermentation may magnify the known benefits of a wide

variety of foods and herbs, influencing the bioavailability
and activity of the chemical constituents. In addition, as our
knowledge of the human microbiome increases (the
intestinal microbiota in particular), it is becoming
increasingly clear that there are untold connections
between the ways in which microbes act upon dietary items
pre-consumption, and in turn, the ways in which these
fermented dietary items influence our own microbiota.”

Selhub et al. Journal of Physiological

Anthropology 2014, 33:2
“We have changed the human diet in such a way that it
no longer feeds the whole superorganism, as it were,
only our human selves. We’re eating for one, when we
need to be eating for, oh, a few trillion.”

― Michael Pollan, Cooked: A Natural History of Transformation

Does a gut microbiota-
targeted nutritional
intervention help?
Chronic fatigue

Intake of natural anti-inflammatory and anti-oxidative

substances such as glutamine, N-acetyl cysteine and
zinc, in conjunction with a “leaky gut diet: over 10-14
months significantly attenuates the initially increased
IgA and IgM responses to LPS of gram negative
bacteria. Over 50% of patients showed a significant
clinical improvement or remission.

Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

Metabolic health

A “gut microbiota-targeted dietary intervention”

specifically developed for the management of chronic
low-grade inflammation and metabolic syndrome was
found to improve gut ecology, decrease intestinal
permeability, reduce plasma endotoxin activity, reduce
inflammatory markers and improve metabolic health
(weight, insulin sensitivity, lipid profiles, and blood
pressure) within 9-weeks in central obese patients.

FEMS Microbiol Ecol. 2014 Feb;87(2):357-67.

QUICK CHART: Pure Encapsulations, Personalised Food Supplements
Options Why use this? Suggested use

Vitamin D3 5000 IU Vitamin D deficiency confirmed or suspected 1 capsule daily for 3-

months (then retest)

Digestive Enzymes Ultra Symptoms worse after eating; cramping, bloating, 1-2 capsules per trigger
urgency, diarrhoea and pain and/ or low fecal elastase-1 meal
(FE-1), and/ or FODMAP (GOS) intolerance

Betaine HCl Pepsin Feeling unusually full after small or moderate-sized meals, 1-3 capsules with
sensation food sits for a long time in the stomach protein-rich meals

Saccharomyces Boulardii Diarrhoea or loose, frequent bowel movements, and/ or 1-2 capsules daily, for at
confirmed or suspected GI pathogens least 4-weeks

L-Glutamine 1,000 Mg, or Intestinal permeability and/ or diarrhea predominant 3-5 capsules/ 1 scoop
L-Glutamine Powder symptoms twice daily, for 8-weeks

ProFlora G.I. Dysbiosis, confirmed on stool analysis or suspected 1 capsule daily, for at
least 4-weeks

Boswellia AKBA Pain, cramping and/ or elevated fecal calprotectin/ 1-2 capsules daily, for at
inflammatory biomarkers least 4-weeks
 QUICK CHART: Pure Encapsulations, Personalised Food Supplements
Options Why use this? Suggested use

MotilPro For treatment or prevention (re-occurrence after 3 capsules 1-2 times

treatment) of SIBO with suspected low gastric transit daily

Metabolic Xtra Berberine has shown compelling evidence for improving 1-3 capsules daily
cardiometabolic health, which may be explained in part
by modification of the microbiota and a reduced
endotoxin reserve

MicroDefense For suspected (clinical symptoms) or confirmed SIBO 2 capsules twice daily
(elevated breath hydrogen or methane) for 30-days (if non
responsive, try A.C.
Formula® II)

Colostrum 40% IgG Colosturm provides lactoferrin and IgG, both of which 1 capsule, 2 times daily
bind endotoxin and prevent absorption. Colostrum may
also reduce gut permeability & allergic inflammation

Resveratrol Extra Suspected low grade post prandial metabolic 1 capsule 10 min prior
endotoxemia, may particularly benefit blood glucose to meals 1-2 times daily
metabolism
“The functional medicine model for health care is less concerned with what we call
dysfunction or disease, and more about the dynamic process that resulted in a
persons dysfunction.” – Jeffery Bland, PhD