Prebiotics, Microbiota-Nourishing Foods, and Synbiotics

Question 1

Define prebiotic.

Answer 1

a substrate that is selectively utilized by host microorganisms
conferring a health benefit

Question 2

4 conditions to be classified as a prebiotic:

Answer 2

1. Neither be hydrolysed nor absorbed in the stomach or small
   intestine;
2. Act as a selective substrate for one or a limited number of
   potentially beneficial commensal bacteria in the large
   intestine;
3. Change the colonic microbiota ecosystem towards a healthier
   composition; and
4. Induce luminal or systemic changes that improve the health of
   the host

Question 3

3 major prebiotic compounds?

Answer 3

1. FOS - inulin-type fructans
2. Galactooligosaccharides
3. Lactulose

Question 4

FOS food sources examples

Answer 4

Garlic, onion, Jerusalem
artichokes, chicory root

Question 5

GOS food sources examples

Answer 5

Cow’s milk (traces)

Question 6

Lactulose food sources examples

Answer 6

UHT milk (traces)

Question 7

FOS targeted microbes

Answer 7

Bifidobacteria, Faecalibacterium, &
Akkermansia

Question 8

GOS targeted microbes

Answer 8

Bifidobacteria & Faecalibacterium

Question 9

Lactulose targeted microbes

Answer 9

Lactobacilli, Bifidobacteria, &
Faecalibacterium, Akkermansia

Question 10

Partially-hydrolysed Guar Gum targeted microbes

Answer 10

Bifidobacteria & multiple butyrate-producing species

Question 11

Acacia fibre targeted microbes

Answer 11

Increase in bifidobacteria, lactobacilli and Bacteroides populations

Question 12

Choosing the right prebiotic considerations?

Answer 12

Patient factors
* dysbiotic picture
* tolerance to intestinal gas production

Your treatment goals
* additional therapeutic impact beyond just prebiotic effects
* take into account unique actions of differing prebiotics

Question 13

Three types of FOS, delineated by their size?

Answer 13

• inulin - the largest FOS; typically extracted from chicory roots
  using only hot water
• oligofructose - a medium-chain FOS; produced from inulin
  using enzymatic hydrolysis
• neosugar - a short-chain FOS; synthesised using a fungal
  organism that converts sucrose to FOS

Oligofructose-enriched inulin – equal parts inulin and
oligofructose

Question 14

What are the uses of FOS?

Answer 14

*1. Enhancement of Immunity
Administration to toddlers (7-19 month olds) resulted in a
significant reduction in: (Waligora-Dupriet et al, 2007)
* number of infectious diseases requiring antibiotic treatment (P<0.001)
* episodes of diarrhoea and vomiting (P<0.001)
* episodes of fever (P<0.05)

2. Enhanced absorption of calcium (Griffin et al, 2002)
3. Improved bioavailability of phytoestrogens (Uehara et al, 2001)
4. Prevention of atopy development (Moro et al, 2006)
5. Promotion of satiety (Cani et al, 2006)
   * Improved blood sugar control in diabetes (Colantonio et al, 2020)
6. Improved efficacy of medicinal herbs?
   - upregulates β-glucosidase activity

Question 15

What is lactulose?

Answer 15

1. Lactulose is a semi-synthetic disaccharide composed of
   the monosaccharides fructose and galactose
   * indigestible to human digestive enzymes
   * manufactured via the heating of lactose (milk sugar)
   * found in small amounts in UHT cow’s milk

Question 16

Conditions/issues that can be helped by lactulose?

Answer 16

1. Candidiasis (GIT)
2. Constipation
3. Alcoholic liver disease
   
   • particularly to prevent or treat hepatic encephalopathy
4. Prevention of colon cancer
5. Damaged intestinal or colonic mucosa
6. trophic and healing effects in the small and large bowel
7. Colon acidifier
8. To decrease endotoxin exposure & absorption
9. Enhances calcium absorption (Seki et al, 2007)
10. Prevention of urinary tract infections (Mack et al, 1993)
11. Vaginal dysbiosis (Collins et al, 2018)
12. vaginal candidiasis
13. bacterial vaginosis
14. Ulcerative colitis

Question 17

describe Galactooligosaccharides (GOS)

Answer 17

Non-digestible carbohydrates
* produced from lactose using β-galactosidases

These β-linked glycosides are resistant to digestion by
host-secreted enzymes in the small intestine
* reach the terminal ileum & colon intact
* become available to those members of the colonic microbiota
metabolically equipped to metabolise these specific
oligosaccharides

Question 18

uses of GOS

Answer 18

• Treatment of constipation
  
  • elderly subjects over 2 wk period (Teuri & Korpela, 1998)
    
    • ↑ in defecation frequency (from 5.9 to 7.1
      movements/week)
      
      • trend for easier defecation (P=0.07)
• Increased resistance to infections
  * in combo with FOS added to formula (Arslanoglu et al,
  2007)(Bruzzese et al, 2009)
• Improved absorption of calcium
• Metabolic Syndrome
  12 wks txt resulted in significant decreases in:
  * serum CRP (P<0.0012)
  * serum insulin (P<0.005)
  * total cholesterol (P<0.001)
  * triglycerides (P<0.0005)

Question 19

GOS & FOS and Stress

Answer 19

• GOS and FOS+GOS attenuated acute stress-induced
  corticosterone release
• GOS and FOS+GOS reduced the number of stress-induced
  bowel movements
• FOS+GOS reduced chronic stress-induced elevations in
  corticosterone, and inhibited release of pro-inflammatory
  cytokines
  * IL-6 and TNF-α
• FOS+GOS administration significantly increased
  hippocampal brain-derived neurotrophic factor gene
  expression, GABAB1 receptor gene and GABAB2
  receptor gene
• FOS and FOS+GOS administration increased serotonin
  levels in the prefrontal cortex
• FOS+GOS reduced depression-like and anxiety-like
  behaviour
• FOS+GOS also minimised the negative impact of
  chronic stress on the microbiota
• Protected populations of bifidobacteria and lactobacilli

Question 20

GOS and the Stress Response

Answer 20

• Morning Cortisol
• Salivary cortisol awakening response was significantly
  lower after 3 weeks of GOS intake
• Emotional Processing
• Increased processing of positive vs negative attentional
  vigilance

Question 21

Uses of Galactooligosaccharides

Answer 21

Treatment of irritable bowel syndrome
* 3.5g/day
* improvement in stool consistency, flatulence scores,
bloating scores, and overall IBS symptom scores
compared to placebo (all P<0.05)
* 7.0g/day
* improvements in overall IBS symptom scores and a
reduction in anxiety levels compared to placebo (both
P<0.05)
* increase in bloating scores relative to baseline (P<0.05)

Prevention of GIT Infections
* reduces adherence of pathogenic strains of Escherichia coli
to gastrointestinal cells (Shoaf et al, 2006)
* inhibits binding of Vibrio cholera toxin to its receptor in the
human GIT (Sinclair et al, 2009)
* reduces colonisation and pathology associated with
Salmonella typhimurium infection in a murine mode

Prevention of Traveller’s diarrhoea

IRON absorption - ferrous fumarate
Iron supplementation can cause dysbiosis (e.g., a bloom of
Enterobacteriaceae) (Jaeggi et al, 2015)
* this dysbiosis can be attenuated by co-supplementing GOS

Question 22

What prebiotic combination is good for wrinkles?

Answer 22

Lactulose and GOS combination

Question 23

What are HMOs?

Answer 23

Human Milk Oligosaccharide
HMOs are a group of complex sugars that are abundant in
human milk (Bode, 2006)(Bode, 2015)
* each mother has a unique pattern of HMOs
* change over the course of lactation
* more than 200 HMOs discovered to date!
* only present in infinitesimal amounts in bovine milk vs 5-15g/L in human milk

• Like other prebiotics, HMOs are minimally digested by
  humans (Gnoth et al, 2000)
• HMOs have recently become commercially-available
• generally chemically synthesised or enzymatically-derived from
  bovine milk (Perna et al, 2023)(Zeuner et al, 2019)
• 2’-fucosyllactose (2’FL); lacto-N-neotetraose (LNT)

Question 24

HMO effect on microbiota?

Answer 24

• significant increase in diversity of the ecosystem (P=0.004)
• notable incr in SCFAs with 2’FL

Question 25

HMOs uses?

Answer 25

Dysbiosis
* targets Bifidobacterium almost exclusively

IBS
* in the 5g/d group, the only change was an increase in
bifidobacteria
* in the 10g/d group, there were increases in:
* Bifidobacterium, Alistipes, Bacteroides, Prevotella and
Parabacteroides

Question 26

What are XOSs

Answer 26

Xylooligosaccharides (XOS)
XOS are mixtures of oligosaccharides containing β-1,4-
linked xylose residues
* Naturally found in trace amounts in bamboo shoots, fruits,
vegetables, and honey (Vazquez et al, 2000)
* Commercially, generally made from agricultural residues

Question 27

XOS – Effects on the Microbiota?

Answer 27

increased bacterial counts of Bifidobacterium (culturing)
* reduction in stool pH – from 7.39 to 6.50 (P<0.05)
* increase in fecal moisture – 71.1% to 78.9% (P<0.05)
increased fecal concentrations of butyrate and β-glucuronidase

Childs et al (2014)
* 8g/d for 3 wks in healthy adults
* increased mean bowel movements per day (P=0.009)
* did not alter symptoms of bloating, abdominal pain, or flatulence
* improved self-reported vitality (P=0.003) and happiness
(P=0.004)
* increased populations of Bifidobacterium

Finegold et al (2014)
* 1.4g or 2.8g/d for 8 wks in healthy adults
* both grps had significant increases in Bifidobacterium
populations, with a clear dose response noted
* no changes in Lactobacillus, Clostridium, or Enterobacteriaceae
populations
* increased levels of Bacteroides fragilis in the 2.8g/d grp
* No changes in stool pH or SCFA concentrations in stool

Lin et al (2016)
* 1.2g/d for 6 wks in healthy adults
* increased bacterial counts of Lactobacillus and Bifidobacterium
(culturing)
* reduction in Clostridium perfringens populations
* no changes in coliforms (e.g., E. coli, Klebsiella, etc…

Question 28

Conditions that benefit from XOS

Answer 28

• Dysbiosis
• lack of bifidobacteria
• low levels of Bacteroides
• Constipation
• Pregnant women with severe constipation (n=29) (Tateyama et al, 2005)
• 4.2g XOS per day for 4 wks
• stool frequency increased from 1.1/wk at baseline to 5.3/wk at the end of
  week 1, 5.9/wk by week 2, 6.2/wk by week 3, and 6.7/wk by the end of
  week 4
• improvements in distension, bloating and abdominal pain
• no side effects reported

Diabetes Support (Sheu et al, 2008)
* R, DB, PC trial; n=26 patients with diabetes
* 4g/d XOS or placebo for 8wks

Question 29

What is PHGG?

Answer 29

Partially-Hydrolysed Guar Gum (PHGG)

• Natural dietary fibre with prebiotic-like qualities
• Derived from the guar bean (Cyamopsis tetragonoloba) via controlled enzymatic hydrolysis
• Used in the treatment of a number of GIT disorders
  * diarrhoea of many causes; functional constipation; SIBO;
  IBS

Question 30

PHGG – Effects on the Microbiota

Answer 30

• increases in populations of Bifidobacterium and Lactobacillus
• no significant changes in yeast, mold, Bacteroides or Enterobacteraceae
  populations
• reduction in beta-glucuronidase activity and stool ammonia levels
• reduction in stool pH – from 6.15 to 5.77
• increases in the amount of bacterial butyrate-producing genes
  in the stool and concentrations of butyrate producers
  * Clostridium coccoides group, the Roseburia/ Eubacterium
  rectale group, Eubacterium hallii, and butyrate-producing
  bacterium SS2/1
• Yasukawa et al (2019)
• 5g/d in healthy subjects (with a tendency towards softer stools –
  Bristol types 5 and 6) for 3 months
• stool form normalised with treatment (e.g., moved towards
  Type 4)
• increased populations of:
• Bifidobacterium
• Ruminococcus
• Megasphaera
• decreased populations of:
• Bacteroides

Kapoor et al (2020)
* 6g/d in healthy athletes for 4 wks
* significant reduction in diarrhea episodes with use
* significant increase in bifidobacteria
* decreases in both Bacteroides and Prevotella populations

Question 31

PHGG - Uses

Answer 31

• Dysbiosis
• lack of butyrate-producing species
• lack of bifidobacteria
• lack of lactobacilli (larger doses only)
• To enhance butyrate generation in the colon
• IBS
• Systematic review of PHGG in IBS trials (Hawrelak & Whitten, 2016)
• all 9 studies produced positive findings
• improvements in IBS symptoms and bowel pattern
• improvements in mood and QoL
• improvements noted in all sub-types of IBS

Autism Spectrum Disorder
* defecation frequency improved from 1.3/wk to 2.8/wk (P<0.01)
* Aberrant Behaviour Checklist – significant improvement in irritability
subscale (P<0.01)
* increase in butyrate-producing bacterial species
* Acidaminococcus, Blautia, & Fusicatenibacter
* decreases in Streptococcus, Alistipes, and Bacteroides
* reduction in serum inflammatory markers
* IL-1β, IL-6, TNF-α (P=0.07

Constipation (Kapoor et al, 2017)
* systematic review and meta-analysis found PHGG effective in
improving fecal defecation frequency, fecal volume, fecal
weight, and fecal moisture content
* 5-7g/d generally enough to work, but it looked like higher
doses were likely more effective

Skin hydration (Kapoor et al, 2023)
* R, OL trial in healthy subjects (n=49)
* 12 wks supplementation with PHGG (either 6g or 12g/d)
* both doses significantly improved skin hydration by helping to
maintain consistent moisture levels in the surface skin stratum
corneum

Ileostomy support (Ho et al, 2022)
* n=29 patients post-op colorectal cancer with ileostomies
* 7.6g PHGG/d

• Improved fertility outcomes in females with infertility (Komiya et
  al, 2020)
• 12 patients received combined therapy comprising embryo
  transfer by assisted reproductive technology and oral
  supplementation with PHGG (10g/d) for 4 wks
• the success of pregnancy by this combined therapy was 58.3%
  (7/12)
• usual success rate is ~36%
• Immune support
• Influenza prevention (Takahashi & Kozawa, 2021)
• retrospective study comparing hospitalised patients taking daily PHGG and
  those not over a 2-month period

Immune support
* reduction of cold-like symptoms (Sakai et al 2022)
* R, DB, PC trial in healthy adults (n=96)
* 12 wks supplementation with either placebo or 5.2g PHGG
* Cold-like symptoms assessed by a symptom diary

Metabolic dysfunction
* reduction in waist circumference and glycated Hb (HbA1c) after
6 wks taking 10g/d (Dall’Alba et al, 2013)
* 6g with each main meal (so 18g/d) for 12 months (Kapoor et al, 2016)
* significantly lowered the postprandial plasma glucose, reduced both the
fasting and postprandial insulin and TG levels (all P=0.05)
* LDL was lower and HDL levels higher (P<0.01).
* plasma leptin, hs-CRP and fasting glucagon like peptide were also
decreased

Promotion of Satiety (Rao et al, 2015)
* induces both acute and longer-term satiety
* reduces energy intake from snacking

Intestinal Methanogen Overgrowth (IMO) (Furnari et al, 2012)
* colonic and small bowel

Diarrhea
* athlete’s diarrhea (runners diarrhea) (Kapoor et al, 2020)
* healthy people with softer stools (Type 5-6) (Yasukawa et al, 2019)
* sugar alcohol-induced diarrhea (Nakamura et al, 2007)

Pediatric functional abdominal pain (Romano et al, 2013)

Question 32

Which prebiotics or prebiotic like substances are less likely to cause gas related side effects?

Answer 32

Acacia fiber, PHGG, HMOs and to a lesser degree, GOS

Question 33

What’s not a Prebiotic?

Answer 33

Commonly used fibre supplements, such as slippery elm,
pectin, psyllium husks, flaxseeds should all be considered
colonic foods or microbiome-nourishing fibres, not
prebiotics, as they are utilised by a wide number of different
bacterial species in the bowel

Question 34

define prebiotic-like food

Answer 34

Some foods have demonstrated the ability to promote
the growth of beneficial species of bacteria
* although their effects may not be as specific as with prebiotics

Question 35

define synbiotics

Answer 35

Synbiotics are: a mixture comprising live microorganisms
and substrate(s) selectively utilized by host
microorganisms that confers a health benefit on the host

Question 36

4 factors/characteristics of synbiotics

Answer 36

• does the product use well-characterised and researched
  probiotic strains?
• does the “prebiotic” substance meet the requirements to be
  truly considered a prebiotic?;
• has the “prebiotic” been demonstrated to enhance the growth of
  the exact probiotic strain(s) contained in the product?
• are both agents included in therapeutic doses?

Question 37

Bifidobacterium lactis Bb12 can utilise what prebiotics?

Answer 37

GOS, lactulose and FOS,
but is unable to use lactitol

Question 38

Lactobacillus rhamnosus GG is UNABLE to use WHAT PREBIOTIC?

Answer 38

e lactulose, lactitol or
FOS

Question 39

definitions for Postbiotics

Answer 39

• Postbiotics are byproducts of the fermentation process carried out by
  probiotics in the intestine
• Non-viable metabolites produced by probiotics that exert biological
  effects on the host
• Also called “short chain fatty acids”
• Postbiotics are bioactive compounds made when the healthy bacteria
  in your gut… feed on various types of prebiotic food in your colon,
  such as fiber
• The term is inconsistently used and lacks a clear definition