Figure . . Pathophysiology of Increased Intestinal Permeability.

Alteredintestinal

permeability

Poor dietary choices

Stress & emotions

Infection

Lectins

Systemic disease

Toxic exposure

Food allergy

Altered intestinal permeability: Pathophysiology

Malnutrition

Dysbiosis

Toxic overload

Elevated totaltoxic & antigenicburden

Low stomach acidSystemic disease

Figure . . Intestinal Barrier Defenses in the Healthy Gut. Th e gut lining functions as a selective gate or barrier, allowing the passage and transport of small and medium-sized molecules of essential nutrients and communication peptides. At the same time, the membrane bars the passage of larger molecules, including many toxins and aller-genic substances. Th e cells of the gut lining play an essential role in this process by allowing some substances through and barring others.

Figure . . Injury to the Intestine and Altered Permeability. Damage to the gut can cause defects to its barrier function with resultant systemic dissemination of toxic bacterial by-products and food antigens.

Effector cells (TH1 or TH2)

Mucosal homeostasis

Regulatory cells

Mucosal inflammation Mucosal inflammation

Figure . . Gut Flora and Intestinal Proinfl ammatory Responses. As a consequence of disruptions in the bacterial fl ora of the gut, mucosal infl ammation can be divided into two categories with respect to eff ector versus regulatory T-cell imbalance. In the fi rst type, bacterial-drive responses are abnormally robust and the intrinsic homeostasis of the mucosal immune system (regulatory) is overwhelmed, and there is a bias towards infl ammation. Alternatively, eff ector-cell responses to gut fl ora can be normal, but regulatory-cell responses (i.e., genetically determined) can be weak; again, infl amma-tion is the result. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology (Bouma G & Strober W. Nat Rev Immunol. July 2003;3:524), copyright 2003.

Figure .. Schematic representation of the pattern of bidirectional brain– gut–microbe interactions. Th e brain can modulate various functions of the gut, as well as the perception of gut stimuli, via a set of parallel outfl ow systems that are referred to as the EMS, which include the sympathetic and parasympathetic branches of the ANS, the HPA axis, and endogenous pain-modulation systems. (Mayer, 2000) Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Gastroenterology and Hepatology (Rhee et al., Nat Rev Gastroenterol Hepatol . 2009 May;6(5):306–314) Copyright 2009.

Direct and indirectmodulation of entericmicrobiota bythe CNS

Modulationof nervous

system functionby enteric microbiota

Visceral stimuli perceptionemotion

GI motility, secretion,permeability

ANS HPA axis

Viscerosensorymechanism

Mucosal immunefunction

Enteric microbiota

EMS

Luminal stimuliECCs

5-HT5-HTCRF?SST?Dynorphin?

Regulation of entericmicrobiota behavior?

Hormonal andimmune signals

SNS Neuralsignals

Hormonal andimmune signals

Endocrinehormones

Capilla

ry

Axonreflex

Figure .. Enterochromaffi n cells as bidirectional signal transducers between host and enteric microbiota. Reprinted with permission from Furness, J. B. & Clerc, N. Prog. Brain Res. 1999; 122:159–172.

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