Presentazione a cura del Professor Davide Festi - M.A.S.T.E.R. ECM in Gastroenterologia Focus on: Microbiota e dintorni - Fondazione Santa Lucia - Roma

1. Dieta e microbiota intestinale: quale
rapporto
Davide Festi, Ramona Schiumerini
Dipartimento di Scienze Mediche e Chirurgiche
Università di Bologna
davide.festi@unibo.it
M.A.S.T.E.R. ECM in Gastroenterologia 2018
Focus on: Microbiota e dintorni
Roma, 9 Febbraio 2018

2. Gut microbiota
Definition
• Human gut microbiota: complex and dynamic
ecosystem, residing in human gastrointestinal
tract, composed by different microorganisms,
living in a symbiotic relationship with the host.
• Composed by hundreds to thousands of
bacterial species, viruses, archaea, yeasts
and protozoa.
• The collective genome of host’s indigenous
microbes constitutes the “microbiome”.
• Gut microbiota: a sort of “metaorganism”,
exerting a great influence on host’s organism
functions.
Hooper (2001);Van Best (2015)

3.  Barrier function and protection against pathogens
 Maturation and modulation of immune system
 Metabolic functions
 Promotion of mucosal trophism
 Influence on neurological health and performance
Gut microbiota
Beneficial functions in host organism

4. Gut microbiota
Microbiome and host:
a mutualistic relationship
• Microbiome ferments substrated that humans cannot and
produces biologically active metabolites
Hurst NR, 2014
• Microbiome has a bidirectional relationship with the
endocrine system
Neuman H, 2015
• Microbiome has genes not possessed by humans
Harvil R, 2016

5. Gut microbiota
Factors affecting composition
• Host genotype
Benson AK, 2010
• Age
Yatsumenko T, 2012
• Sex
Bolnick DI, 2014
• Environmental factors
Voreades N, 2014

6. Gut microbiota
Diet and gut microbiota
J Med Res 1919; 39: 415-447

7. Gupta VK, Front Microbiol 2017
Gut microbiota
Population-specific variations in human
microbiome composition and diversity

8. Changes in dietary habits bring human species evolution  changes in gut
microbiota composition.
Studying populations with different dietary habits, from hunter-gatherers
to rural farming and industrial agriculture, it’s possible to understand the
progressive adaptation of gut microbiota to dietary changes.
Progressive↓ of bacterial diversity and fibrolytic micro-organisms such as
Proteobacteria and Spirochaetes, in parallel with ↑ Actinobacteria.
Diet and gut microbiota
Evolution of gut microbiota in parallel with dietary habits
Schnorr, 2014; He, 2013

9. Diet and gut microbiota
Gut microbiome of the Hadza hunter-gatherers
(Hazda = 27; Italians = 16)
Metabolite production
(Hazda: orange; Italians: blue)
Bacterial relative abundance: Hazda vs Italians
Schnorr SL, Nat Comm 2014

10. Diet and gut microbiota
Dietary habits, geographical origins and gut microbiota
Comparison between fecal microbiota of Burkina Faso (BF) children and European
(EU) children:
• High fiber diet of BF children promotes ↑Bacteroidetes (in particular genus of
Prevotella, Xylanibacter) that hydrolize complex starch
• Low fiber diet of EU children is associated to relative ↑Firmicutes and
Enterobacteriaceae (Shigella and Escherichia)
De Filippo C et al, Proc Natl Acad Sci 2010

11. Diet and gut microbiota
Dietary habits, geographical origins and gut microbiota
Native AfricansAfrican Americans
High CCR risk Low CCR risk
Ou J et al,Am J Clin Nutr 2013
↑ protein and fat consumption ↑ complex starch consumption
↑ bacteria capable of proteolytic fermentation
(Bacteroides)
↑ bacteria capable of polysaccharide fermentation
(Prevotella)
↑ microbial genes encoding for secondary bile acid
production (pro-inflammatory)
↑ production of SCFAs (i.e. anti-inflammatory
butyrate)

12. Diet and gut microbiota
Gut microbiota and host subsistence strategies
Gupta VK et al Front Microbiol 2017

13. Diet and gut microbiota
Human gut microbiota through life stages

14. Diet and gut microbiota
Gut microbiota during antenatal period
• Presence of bacteria in the amniotic fluid, placenta, cord blood, meconium
Jemenez E, 2005; Di Giulio DB, 2012; Moles L, 2013
• Mother’s diet before and during pregnancy influences child gut microbiota
development 
Mother’s diet Influences in child gut microbiota
• maternal gluten-free diet   Achermansia and Proteobacteria
• unhealthy mother’s diet  Inadequate gut microbiota composition and
functionality
• oil fish consumption  positive effects on intestinal microbiota
Boscia AL, 2014; Myles A, 2014; Hansen CH, 2014

15. Diet and gut microbiota
Mother-infant relationship
Nash MJ et al, Front Endocrinol 2017

16. Power, 2014
Diet and gut microbiota
Human gut microbiota through life stages

17. At the end of the first 3 years of life gut microbiota  an adult-like stable system.
• 60-70% of the microbiota composition remains stable throughout life.
• 30-40% can be altered by changes in the diet, physical activity, lifestyle, bacterial
infections, and antibiotic or surgical treatment.
Kashtanova, 2016
Diet and gut microbiota

18. • Gut microbiota rapid turnover (doulble within 1hr)
(Sonnenburg JL, 2016)
• Diurnal oscillations driven primarly by food intake rhythm
(Zarrinpar, 2014)
• Gut microbiota responds rapidly to large changes in diet (short
term and long-term responders)
(Wu GD, 2011, Arumugam M, 2011; David LA, 2014)
• Long-term dietary habits  composition of an individual’s gut
microbiota
(Wu GD, 2011, 2016)
Diet and gut microbiota

19. Even if microbiome composition changes detectably within 24 hours of initiating a 10-day
controlled diet (high-fat/low-fiber or low-fat/high-fiber diet) the enterotype identity
remains stable Wu GD et al. 2011
Diet and gut microbiota
Short-term influence of diet variation

20. Diet and gut microbiota
The concept of enterotypes
“Enterotypes”: clusters of predominant microbial species reflecting a
host-microbial symbiotic state, influenced by diet.
• Enterotype 1: predominant genus: Bacteroides; association with animal
protein rich-diet and saturated fats (Western diet)
• Enterotype 2: predominant genus: Prevotella; association with complex
carbohydrates and simple sugars-rich diet (agrarian societies diet)
• Enterotype 3: predominant genus: Ruminococcus; degrades mucins; derives
energy from simple sugars.
Arumgam M et al. 2011; Wu GD et al. 2011

21. • Little, or no clear, segregation into enterotypes among stool samples of
200 subject
(Huse et al. 2012)
Diet and gut microbiota
The «shadows» of enterotypes concept
• Only two distinct clusters enterotypes (Prevotella and Bacteroides),
because the third enterotype dominated by Ruminococcus appeared to be
fused with Bacteroides (Wu et al. 2011)
• Not fixed entities, but a continuous gradient
(Wu GD, 2011; Jeffery IB, 2012; Koren O, 2013; Knights D, 2014)

22. Diet and gut microbiota
Effects of protein on gut microbiota
Singh RK etal, J Transl Med 2017

23. Diet and gut microbiota
Effects of fats on gut microbiota
Singh RK etal, J Transl Med 2017

24. Diet and gut microbiota
Effects of natural and artificial sugars and of non-
digestible carbohydrates on gut microbiota
Singh RK etal, J Transl Med 2017
NATURAL AND ARTIFICIAL SUGARS
NON-DIGESTIBLE CARBOHYDRATES

25. Diet and gut microbiota
Effects of diets on gut microbiota
Singh RK etal, J Transl Med 2017

26. Diet and gut microbiota
Limits of studies
1. Several studies on animals but few studies on human subjects.
2. Fecal samples are less representative of sites of active food fermentation
(cecum and proximal colon).
3. High variability of diet and lifestyle between studied subjects.
4. Scarce evidence about long term effects of diet.
5. Bias of interpretation of results due to physiologic inter-individual variability.
6. A common agreement on the definition of «healthy microbiota» doesn’t exist
Additional well designed studies, exploring variability and modification of
microbial functionality rather than its mere composition are needed.
Graf, 2015

27. Diet and gut microbiota
Role of microbiota biodiversity
• modern diet  ↓ agrobiodiversity
(FAO, 2004)
• ↑ widespread of antibiotics and pesticides  ↓microbiota richness
(Cho, 2012)
• Gut microbiota richness is well correlated with health
(Chatelier, 2013)
• More diverse is diet, more diverse is microbiome, more adaptable
to perturbations (Heiman, 2016)
• Microbial biodiversity  strictly related to its functional richness
↑ adaptability to perturbations (Heiman, 2016)

28. Diet and gut microbiota
Decreased agrobiodiversity
• 75% of plant genetic diversity has been lost;
• Humans use 150-200 edible plant species of the 250-300.000 known;
• 75% world’s food is generated from 12 plants and 5 animal species.
FAO, 2004

29. Diet and gut microbiota
Microbiota diversity and disease
Mosca A et al, 2016

30. Diet and gut microbiota
Gut microbiota in health and disease
Cerf-Bensussan, 2010

31. Diet and gut microbiota
Diet, dysbiosis and metabolic disorders
Ojeda P, 2016

32. Diet and gut microbiota
Overweight and obesity

33. Diet and gut microbiota
Microbiota, energy homeostasis and high fat diet
Mulders et al, Obes ev 2018

34. Insulin
resistance
and type 2
diabetes
LPS induced
systemic low
grade
inflammation
↑intestinal
permeability
Alteration of
bile acid
metabolism
↑activity of
endocannabinoid
system (eCB1)
HFD, artificial sweeteners,
emulsifiers
Genetic susceptibility
(TLR-4, TLR-5, CD-14)
Cani, 2007; Vrieze, 2013; Scheithauer, 2016
↓butyrate producing and anti-inflammatory bacteria
(Roseburia, F. prausnitzii, Akkermansia muciniphila)
↑ Gram negative bacteria,
Enterobacteriaceae,
Proteobacteria
Diet and gut microbiota
Gut microbiota, insulin resistance and
diabetes

35. Bajaj JS, Hepatology 2018, in press
• Microbial diversity was associated with an independently lower risk
of 90-day hospitalizations.
• Diet rich in fermented milk, vegetables, cereals, coffee and tea, is
associated with a higher microbial diversity
Diet and gut microbiota
Diet, gut microbiota and liver cirrhosis
296 subjects
157 USA:48 controls, 59 compensated, 50 decompensated;
139 Turkey:46 controls, 50 compensated, 43 decompensated)

36. Diet and gut microbiota
Complex interplay between gut, brain and adipose tissue
Influence of gut microbiota on
central nervous system function:
• production of substances
interacting with terminal
nerve (NO or GABA);
• ematoencefalic membrane
permeability;
• modulation of appetite and
satiety (GLP-1, peptide YY and
ghrelin).
Influence of central nervous
system on microbiota
composition:
• mucin production and gut
epithelial function;
• gut motility.
• local immune response
Ghaisas, 2016; Cani, 2016; Machado, 2016
Leptin and adipokine modulate both
appetite and gut microbial composition
(affecting production of antimicrobial
peptide by Paneth cells)

37. Diet and gut microbiota
Western diet, gut microbiota and
cognitive dysfunction
Noble E et Al, Front Behav Neurosci 2017

38. Gut Microbiota in Obesity and Metabolic Abnormalities
A Matter of Composition or Functionality?
Moran-Ramos S, Arch Med Res 2017

39. Diet and gut microbiota
How to manipulate gut microbiota
1. Probiotics: live micro-organisms which, when administered in adequate
amounts, confer a health benefit on the host.
 Psychobiotics: live bacteria which, when ingested, confer mental
health benefits through interactions with commensal gut bacteria.
2. Prebiotics: selectively fermented ingredients that allow specific changes,
both in the composition and/or activity in the gastrointestinal microflora
that confer benefits upon host well-being and health.
3. Antibiotics
4. Fecal microbiota transplantation: transfer of fecal material containing
bacteria and natural antibacterials from a healthy individual into a
specific recipient.

40. Cell 2015;163:1079-1094
Diet and gut microbiota
Personalized Nutrition by Prediction of
Glycemic Responses

41. Diet and gut microbiota
Take home message
• Gut microbiota is a complex “metaorganism” which exerts a great
influence on host’s homeostasis.
• Genetic and environmental factors affect its composition, during all
stages of life. Diet seems to represent the most influent
determinant.
• Even if gut microbiota composition rapidly responds to dietary
changes, long-term dietary habits seem to really delineate its
identity.

42. • gut microbiota biodiversity  its adaptability to external
perturbations  affects host’s homeostasis.
• gut microbial composition as predictor of response to dietary
therapeutical strategies  personalized therapeutical plan
• gut microbiota manipulation techniques  potential therapeutical
option
Diet and gut microbiota
Take home message
• diversified diet  gut microbiota biodiversity and richness.
• dysbiosis, plus to host’s genetic and environmental factors (e.g.
diet)  development of several diseases.

43. Dieta e microbiota: quale rapporto?
Grazie per l’attenzione

44. • Short term diet-induced changes of gut microbial composition are mostly influenced by a
strict animal-based diet vs plant-based diet
• A significant modification of gut microbial composition from baseline (↑ β-diversity) is
observed only during a shift to animal-based diet.
• Gut microbiota rapidly reverts to its original composition 2 days after diet interruption.
• ↓ Prevotella genus and ↑bile-tolerant microorganisms during fiber restriction.
• ↓ SCFAs production and ↑ protein fermentation during animal-based diet.
David, 2014
Diet and gut microbiota
Short-term influence of diet variation