Corso di laurea in Scienza della Alimentazione e
Nutrizione Umana (SANU)
Prof. Stefano Fiorucci
Apparato digerente
Anatomia e fisiologia
Sintomi
Approccio clinico
Metodiche di studio
1
Small bowel anatomy
3
Small bowel immune system
4
Glucose –endocrine axis
5
6
Carbohydrates
Carbohydrates are the most important energy-containing
components of the diet.
The energetic value of most carbohydrates is 17.5 kJ per g.
A daily diet of 400 g carbohydrates covers 7 000 kJ, which is 56%
of the usable energy in a diet of 12 500 kJ daily. The formation of
metabolic water on a mixed diet is 0.032 g of water per J.
The common sources of digestible carbohydrates are starches
(amylose), table sugar, fruits and milk.
Plant and animal starch (amylopectin and glycogen) are branched
molecules of glucose monomers.
Indigestible carbohydrates are present in vegetables, fruits and grains
(cellulose, hemicellulose, pectin) and in legumes (raffinose).
Indigestible carbohydrates are also referred to as dietary fibres.
Digestion of starches to simple
hexoses occurs in two phases:
The luminal phase begins in the
mouth with the action of salivary
amylase (ptyalin), In the small
intestine The starch polymer is
reduced to maltose, maltriose and
a-limit dextran or dextrins. The
three substrates are pushed through
the intestine and are now ready for
the brush-border phase. Some of
the substrate molecules get into
contact with the brush-borders of
the absorbing mucosal cell via the
unstirred water layer. Enterocytes
carry disaccharidases and
trisaccharidases (oligosaccharidases)
on their surface that cleave these
substrates to glucose, G.
Milk sugar (lactose) and cane sugar (sucrose) only require a brushborder phase of digestion, since they are disaccharides.
Sucrose is reduced to glucose and fructose (G-F),
and lactose to glucose and galactose (G-Ga) by the action of
disaccharidases (sucrase and lactase).
Proteins
The typical Western diet contains 100 g of protein, which is equivalent to an
energy input of 1700 kJ daily, although an adult needs only less than one g pr kg of
body weight. This luxury combustion is an inappropriate use of global resources.
Moreover, a high protein intake implies a long-term risk of uric acid accumulation
from purine degradation ( Meats, fish, eggs, and diary products are high in proteins
and expensive. Vegetable proteins are not as expensive as animal proteins.
Digestion of dietary proteins begins in the stomach, with the action of the gastric
enzyme pepsin (pH optimum is 1), Pepsin is produced from pepsinogen in the
presence of HCl.
Proteins
The digestion is continued in the intestine by proteolytic enzymes of the pancreas.
Enteropeptidase converts trypsinogen to trypsin. Trypsin acts auto-catalytically to
activate trypsinogen, and also convert chymo-trypsinogen, pro-carboxy-peptidases
A/B, and pro-elastase to their active form. When the chyme is pushed into the
duodenum, the pancreatic juice neutralises the chyme and the activity of pepsin is
stopped. The proteolysis in the small intestine plays the major role, because the
digestion and absorption of dietary protein is not impaired by total absence of
pepsin.
Cytosolic peptidases from the enterocytes and brush border peptidases from the
brush borders of the villous cells then cleave the small peptides into single amino
acids (Enteropeptidase, amino-polypeptidase and di-peptidases).
The end products of protein digestion by pancreatic proteases and brush border
peptidases are di- and tri-peptides and amino acids. The cytosolic peptidases are
abundant and particularly active against di- and tri-peptides.
Lipids
The typical Western diet contains 100 g of lipids (3900 kJ)
daily. Most of the dietary lipids consumed are triglycerides
(only 2-4% is made up of phospholipids, cholesterol,
cholesterol esters etc). Lipids would comprise just above 30%
(ie, 100 g = 3900 kJ) of a standard diet of 12 500 kJ daily. An
optimal diet should contain only 20% lipids, such as the lipids
of fish oil and olive oil.
Colon
18
Integrated meta-omics
19
Lepage P et al. Gut 2013;62:146-158
The human GI microbiota
The gene catalogue - characterized by a metagenomic approach - indicates
the microbe genome encodes for 3,364 non-redundant genes suggesting
that no more than ~1,150 bacterial species are abundant enough to be
detected in the feces. With most individuals harboring approximately 160
different bacterial species and 99% of intestinal microbiome derives from
30-40 species
M Arumugam et al. Nature 000, 1-7 (2011) doi:10.1038/nature09944
21
Functional and phylogenetic profiles of human gut microbiome.
The relationship between gut
mirobiota and humans is a
symbiotic relationship.
Though people can survive with
no gut flora, the microorganisms
perform a host of useful functions,
such as fermenting unused
energy substrates, training the
immune system preventing
growth of harmful species,
regulating the development of the
gut, producing vitamins and
producing hormones to direct the
host to store fats.
However, in certain conditions,
some species are capable of
causing diseases
22
M Arumugam et al. Nature 2011 doi:10.1038/nature09944
Enterotypes of the human gut microbiome
23
M Arumugam et al. Nature 000, 1-7 (2011) doi:10.1038/nature09944
The structure of the human intestinal microbiota across the life cycle.
Kostic A D et al. Genes Dev. 2013;27:701-718
24
16S rRNA gene surveys reveal a clear separation caused
by socio-economic factor
High fat/low fiber diet
Low fat /high fiber diet
De Filippo C et al. PNAS 2010;107:14691-14696
BACTERIOID
PREVOTEL
25
26
Science Express on 6 June 2012, doi: 10.1126/science.1223813
Main metabolites
Main Bacteria
Signaling pathways
Short-chain fatty acids (SCFA): acetate, propionate,
butyrate, isobutyrate and others
Clostridial clusters IV and XIVa of
Firmicutes, including species of
Eubacterium, Roseburia, Faecalibacterium,
and Coprococcus
Lactobacillus, Bifidobacteria, Enterobacter,
Bacteroides, Clostridium
Energy source for colonic epithelial cells, antitumor activities on colorectal cancer. Modulate
insulin resistance in metabolic syndrome and type 2
diabetes
Essential for absorption of dietary fats and lipidsoluble vitamins and act as signaling molecule
through FXR, GPBAR1, PXR, VDR and other BARs*
to regulate triglycerides, cholesterol, glucose and
energy homeostasis.
Faecalibacterium prausnitzii,
Bifidobacterium
Impact on lipid and glucose metabolism. Potential
mediators in nonalcoholic fatty liver disease, diet
induced obesity, type II diabetes, and cardiovascular
disease.
AhR ligands. Anti-inflammatory effects. Unknown
metabolic activities
Bile acids: CA, hyocholic acd, DCA, CDCA, α-MCA,
β-MCA, ω-MCA, TCA, GCA, TCDCA, GCDCA, , TαMCA, T-βMCA, LCA, UDCA, hyodeoxycholic acid,
GDCA, TDCA, tauro-hyocholic acid
Choline metabolites: methylamine, dimethylamine,
trimethylamine, trimethylamine-N-oxide,
dimethylglycine, betaine
Indole derivatives: N-acetyltryptophan,
Clostridium sporogenes, E. coli
indoleacetate, indoleacetylglycine, indole, indoxyl
sulfate, indole-3-propionate, melatonin, melatonin 6sulfate, serotonin, 5-hydroxyindole
Vitamins: vitamin K, vitamin B12, biotin, folate,
thiamine, riboflavin, pyridoxine
D-lactate, formate, methanol, ethanol, succinate,
lysine, glucose, urea, α-ketoisovalerate, creatine,
creatinine, endocannabinoids, 2arachidonoylglycerol (2-AG), Narachidonoylethanolamide, LPS, etc.
Bifidobacterium
Polyamines
Campylobacter jejuni, Clostridium
saccharolyticum
Clostridium difficile, F. prausnitzii,
Bifidobacterium, Subdoligranulum,
Lactobacillus
Bifidobacterium, Roseburia, Lactobacillus,
Klebsiella, Enterobacter, Citrobacter,
Clostridium
Phenolic, benzoyl, and phenyl derivatives
Lipids: conjugated fatty acids, LPS, peptidoglycan,
acylglycerols, sphingomyelin, cholesterol,
phosphatidylcholines, phosphoethanolamines,
triglycerols
Bacteroides, Pseudobutyrivibrio,
Ruminococcus, Faecalibacterium,
Subdoligranulum, Bifidobacterium,
Atopobium, Firmicutes, Lactobacillus
Complementary source to endogenous vitamins.
Unclear metabolic effects
Variety of biological functions. Unclear metabolic
Anti-inflammatory and antitumoral effects. Unclear
metabolic effects
PXR ligands. Regulation of xenobiotic metabolism.
Unclear metabolic effects
Anti-inflammatory and pro-inflammatory activities.
Modulation of immune system. Act on insulin
31
receptor and insulin sensitivity. Regulation of
cholesterol and tryglycerols metabolism
The GI microbiota shapes the bile acids
signaling
Fiorucci & Distrutti, Trends Mol Med, 2015 in press
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Science 6 September 2013: Vol. 341 no. 6150
Bidirectional interactions within the gut
microbiota/brain axis
Nature Reviews Neuroscience 13, 701-712 (October 2012) | doi:10.1038/nrn3346
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
34
Bidirectional interactions within the
gut microbiota/brain axis
35
Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015 Mar 2;125(3):926-38. doi: 10.1172/JCI76304.
Endoscopia
Radiologia
Radiologia
Colonscopia virtuale
Videocapsula
Volume e composizione delle secrezioni del tubo digerente
SECREZIONE
Volume
ml/24 h
Saliva
Succo gastrico
Succo duodenale
Succo digiuno-ileale
Bile
Succo pancreatico
500-2000
500-3000
100-2000
100 - 900
500-1000
100 - 800
Na +
K+
Cl HCO3mEq/l mEq/l mEq/l mEq/l
10
60
140
140
140
145
26
10
5
5
5
5
10
130
80
104
100
75
30
30
35
115
DIARREA - 1
Manca una definizione assoluta, perchè disturbo interpretabile molto
soggettivamente
emissione rapida di feci abbondanti e poco formate
Tra liquidi ingeriti, alimenti e secrezioni, ogni giorno percorrono il
tubo digerente circa 10 litri.
- il 90% è assorbito dall’ileo (arrivano al cieco circa 1000 ml)
- il 90% è assorbito dal colon (volume fecale: circa 100 ml)
- il colon può compensare fino a 4-5 litri
Una riduzione anche modesta della capacità di assorbimento colico o
una riduzione importante dell’assorbimento ileale possono provocare
diarrea, ma non tutte le diarree s’instaurano con questo meccanismo
DIARREA - 2
Nella diarrea sono importanti non solo l’osservazione dei caratteri
organolettici (specie presenza di sangue, feci normocromiche o
“biliari”, steatorrea), ma anche ritmi, rapporti coi pasti, durata (diarree
acute o croniche), concomitanza col dolore.
Nel complesso, il sintomo è aspecifico, in quanto riscontrabile in
numerose malattie, per lo più gastrointestinali, o un condizioni non
francamente patologiche (banali intolleranze alimentari, stress, etc.)
CLASSIFICAZIONE DELLE DIARREE
• Osmotiche: lassativi osmotici, malassorbimenti, intestino corto
• Secretorie: enterocoliti batteriche (endotossine), e virali, lassativi
“irritanti”, sali biliari secondari, tumori intestinali ormonosecernenti
• Essudative: M. di Crohn e colite ulcerosa, colite ischemica, colite
postattinica (da raggi),
• Da alterata motilità: colon irritabile, fattori psico-emozionali,
reazioni neurovegetative, stati disendocrini e dismetabolici
CAUSE DI DIARREA CRONICA
STIPSI
Ridotta frequenza dell’evacuazione delle feci con loro permanenza nel
colon o nel retto, associata o meno a difficoltosa evacuazione, in
assenza di quadro occlusivo (distensione addome, alvo chiuso, vomito)
Anche la stipsi si presta a interpretazioni soggettive che ne rendono
difficile la valutazione. Si ammette che si possa parlare di stipsi per
meno di due evacuazioni settimanali, ma esistono evacuazioni, anche
più frequenti, ma molto difficoltose (DISCHEZIA)
Le STIPSI sono di 2 tipi (entrambi nel m. di Hirschprung)
• Origine colica: di solito fattori alimentari, colite spastica, inattività
e invalidità, m. neuromuscolari, stati depressivi, farmaci,
m. disendocrine e dismetaboliche, disagio “ambientale”
Importante: forme idiopatiche, con rallentato transito colico
• Origine ano-rettale (dischezia): numerose condizioni organiche o
funzionali (ipertono del muscolo puborettale, alterazioni
sensibilità o riflessi defecatori, prolasso mucoso, rettocele, etc.