The document discusses the gut microbiota (microbiata), including its functions, development, role in health and diseases, and potential as a diagnostic marker. It provides details on assessing microbiata functions and composition. The gut microbiota plays important roles in immunity, metabolism and digestion. Development of the microbiota is influenced by birth mode and diet. Dysbiosis of the microbiota is associated with various diseases like IBD, obesity and cardiovascular disease. Microbiota products and composition changes could potentially serve as diagnostic biomarkers. While the field of microbiota research has expanded greatly in recent years, the microbiota remains an underappreciated factor in human health.

1. The neglected/forgotten organ
(Microbiata)

2. •Introduction and definition.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut Microbiata and immunity
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

3. ●Microbiota: the community of micro-organisms themselves
●Microbiota diversity: a measure of how many different species and, dependent on the
diversity indices, how evenly distributed they are in the community. Lower diversity is
considered a marker of dysbiosis (microbial imbalance) in the gut and has been found in
autoimmune diseases and obesity and cardiometabolic conditions, as well as in elderly
people
● Microbiome: The genes and genomes of the microbiota, as well as the
products of the microbiota and the host environment” [the collective genomes
of the micro-organisms in a particular environment. Although the composition
of the gut microbiota varies between individuals, the community in each
individual is relatively stable over time.

4. Hillman ET, Lu H, Yao T, Nakatsu CH. Microbial Ecology along the Gastrointestinal Tract. Microbes
Environ. 2017;32(4):300–313. doi:10.1264/jsme2.ME17017

5. Intestinal microbiota
1012-14 microorganisms microorganisms, > 1500 , different species

8. Microbiota diversity—a measure of how many different species and, dependent
on the diversity indices, how evenly distributed they are in the community.
Lower diversity is considered a marker of dysbiosis (microbial imbalance) in the
gut and has been found in autoimmune diseases and obesity and
cardiometabolic conditions, as well as in elderly people
SCIENCE•5 Oct 2018•Vol 362, Issue 6410•pp. 33-34•DOI: 10.1126/science.aau8816

10. Schematic
representation of the
role of the gut
microbiota in health and
disease giving some
examples of inputs and
outputs.
Ana M Valdes et al. BMJ 2018;361:bmj.k2179

11. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

14. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut Microbiata and immunity
•gut microbiota in health and diseases

15. Main beneficial
functions of the
human gut
microbiota. Circles
represent the three
principal classes of
functions performed
by the bacteria that
inhabit the gut.
Arrows represent
causal relationships.
Abbreviation: SCFA,
short chain fatty acid
July 2011Biologics: Targets &
Therapy 5(default):71-86
DOI:10.2147/BTT.S19099

16. Gut–organ axis: a microbial outreach and networking
Letters in Applied Microbiology, Volume: 72, Issue: 6, Pages: 636-668, First published: 29 May 2020, DOI: (10.1111/lam.13333)

17. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

19. Development of the gut microbiome

22. Consistent gut microbiota patterns observed in CS-born infants
compared to vaginally born
. Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498

23. Consistent gut microbiota patterns observed in vaginally
born infants exposed to intrapartum antibiotics compared to
those not exposed to antibiotics
. Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498

24. Temporal development of the relative abundances of the dominant classes
of bacteria in the infant gut in vaginally born, breastfed infants (a) and CS-
born infants (b). CS, C-section.
. Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498

25. Effects of low abundance of bifidobacteria in infants.
. Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498

27. Summary of the Origin & Transmission of the Microbiome

28. . Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498

30. How & Why does the Microbiome Change after its Establishment
The conditions seen in adults are not the same at birth
The stomach and oral cavity pH changes: Compared to
adults, the stomach is less acidic and duodenum less
alkaline to allow more of the maternal antibodies
obtained through suckling to survive
Enterocyte receptors delay their development until after
suckling so attachment by e.g. E. coli is discouraged
Bifidobacteria in human breast milk and Lactobacillus
discourage expansion of Bacteriodetes. Lactic acid
bacteria (Lactobacillus)
lowering the pH of the GIT to favor their own kind
(other Firmicutes) and discourages Bacteriodetes
Total microbiome levels in infants are several logs lower
than is
characteristic for adults
Stomach Duodenum Ileum Colon

31. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

32. The role of the gut microbiota in health and diseases

33. Figure 15–7. The microbiome is implicated in a variety of disorders. Much recent research has found evidence for a role for the microbiome in many
diseases including skin, metabolic, and cardiovascular disease, as well as cancer, infection, and neurodegenerative and psychiatric disorders.

34. Journal of Experimental & Clinical Cancer Research volume 40, Article number: 42 (2021)

36. Proposed mechanism whereby an altered
microbial balance in the gut can A) be driven
by foreign pathogenic invasion and further
increase the likelihood of future infections, and
B) lead to the promotion of carcinogenesis.
Abbreviations: H 2 S, hydrogen sulfide; ROI,
reactive oxygen intermediate.
July 2011;Biologics: Targets & Therapy 5(default):71-86
DOI:10.2147/BTT.S19099

37. July 2011Biologics: Targets & Therapy 5(default):71-86 DOI:10.2147/BTT.S19099

38. The Human
Microbiome and Its
Potential
Importance to
Pediatrics.
CoreenL. Johnson, James Versal
ovic Pediatrics May
2012, 129 (5) 950-
960; DOI: 10.1542/peds. 2011-
2736

39. Ulcerative Colitis (type of IBD) is associated with an unhealthy microbio
and is increasing in developed Western cultures
Before 1960
1960-1979
1980-2008
IBD is multifactorial
Possible Villains
Dietary Changes?
Cultural Changes?
Use of Antibiotics?
[Discussed by David Elliott; Session 3]

40. The Concept of “Good” (Eubiotic) versus “Bad” (Dysbiotic)
The concept derives largely from studies of unhealthy individuals, e.g. patients with
inflammatory bowel disease (IBD), the very old and infirmed, unhealthy infants and
the obese
“Bad” or dysbiosis features a microbiome with:
1. An increase in the Firmicutes to Bacteriodete ratio (shift from 0.5 to 1.6; see
first slide) which means more Clostridiales, Enterococcus and
Ruminococci
2. A decrease in Bacteriodes fragalis which in healthy people stimulate anti-
inflammatory T-cells (Tregs) and
generates SCFA needed for mucosal integrity
3. More Proteobacteria (pathobionts) and less of Bacteriodes in the elderly
(>80 years old) of poor health
4. Colonies of Staphylococcus instead of Bifidobacteria in unhealthy C-section
infants
5. Higher Clostridiales (Firmicutes) in patients with CVD
6. Higher Actinobacteria in patients with periodontal disease (PD)
A “Good” or eubiotic microbiome appears to correlate with a higher proportion of
Bacteriodetes that thrive on and convert complex fibers to SCFA. However, “Good”
versus “Bad” may depend on the circumstances since, children with an enrichment
of Clostridia (Firmicutes) resolve their allergies faster while those with higher levels of
Enterobacteria (E. coli; Salmonella)
Problem: Of the >1000 species, only 2% can be cultured so we do not know what most of the

42. The Microbiome and Cardiovascular disease (C
Important correlations
“Western” diets are linked to Type II diabetes, CVD and “fishy breath”
Vegans and types on a “Mediterranean” diet have less CVD
“Western” diets have less complex fermentable fiber than in “Mediterranean” diet
Trimethylamine (TMA) and TMAO (a TMA oxide)
Dietary carnitine and phosphotidyl choline from red meat and lecithin (eggs) is con
gut microbiome
Blood levels of TMA are strongly linked
to vascular plague formation and CVD
Vegans and herbivores have lower TMA
and TMAO levels than omnivores
TMA, CVD and the microbiome
Less carnitine and more complex fiber
results in more Bacteriodetes
Probiotics (Lactobacilli) are associated with
weight loss but not lowering of TMA
Short ester forms (acetyl-1-carnitine) are
being tested as a competitive dietary
substitute to lower TMAO

43. •Saltzman, E. T. et all. Frontiers in Microbiology. 30 January 2018.
Intestinal Microbiome Shifts, Dysbiosis, Inflammation, and Non-alcoholic Fatty Liver Disease.

45. Antibiotics affect colon flora
Jernberg C, Löfmark S, Edlund C, Jansson J. Long-term impacts of antibiotic exposure on the
human intestinal microbiota. Microbiology (Reading, England). 2010;156:3216–23.

47. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

48. Overview of candidate
biomarkers for diagnosis of gut
microbiota dysbiosis and
associated human diseases.
↓
Biomark. Med. (2021) 15(2), 139–150

49. Biomark. Med.
(2021) 15(2),
139–150

50. •Introduction.
• Methods for assessing microbiata functions
•gut Microbiata functions
•gut Microbiate development
•gut microbiota in diseases
•Microbiota products as a diagnostic markers
•Gut microbiata, is it still neglected?

51. The microbiome field has exploded in recent years.
March 2018; mSystems 3(2):e00179-17

52. The increasing number of publications on
microbiota/microbiome worldwide
February 2021 ;Qatar Medical Journal 2020(3):4

53. Microbiata is not longer forrgoten
THANK YOU