Changes

*When ARD was first recognised, it was thought to resemble human small intestinal bacterial overgrowth which is caused by an absolute increase in the number of intestinal bacteria.  When duodenal juice was cultured however, it was found that there was a large overlap in bacterial numbers between normal dogs and those with ARD, suggesting that the syndrome resulted either from an alteration in the species distribution of the flora or from a change in the host response to intestinal bacteria<ref name="two">Willard MD, Simpson RB, Fossum TW, Cohen ND, Delles EK, Kolp DL, Carey DP, Reinhart GA. '''Characterization of naturally developing small intestinal bacterial overgrowth in 16 German shepherd dogs.''' ''J Am Vet Med Assoc. 1994 Apr 15;204(8):1201-6.''</ref>.  Different samples from the same animal also gave very different results when cultured, even when the samples were apparently collected at the same time and from the same location.  Some animals were found to fulfill the microbiological criteria of SIBO but not to have any clinical signs.  These discrepancies in the traditional view of SIBO in small animals led to a renewed interest in interaction between the bacterial flora and the mucosal immune system, the collective term for the cells and immune structures located in the GI tract.

*When ARD was first recognised, it was thought to resemble human small intestinal bacterial overgrowth which is caused by an absolute increase in the number of intestinal bacteria.  When duodenal juice was cultured however, it was found that there was a large overlap in bacterial numbers between normal dogs and those with ARD, suggesting that the syndrome resulted either from an alteration in the species distribution of the flora or from a change in the host response to intestinal bacteria<ref name="two">Willard MD, Simpson RB, Fossum TW, Cohen ND, Delles EK, Kolp DL, Carey DP, Reinhart GA. '''Characterization of naturally developing small intestinal bacterial overgrowth in 16 German shepherd dogs.''' ''J Am Vet Med Assoc. 1994 Apr 15;204(8):1201-6.''</ref>.  Different samples from the same animal also gave very different results when cultured, even when the samples were apparently collected at the same time and from the same location.  Some animals were found to fulfill the microbiological criteria of SIBO but not to have any clinical signs.  These discrepancies in the traditional view of SIBO in small animals led to a renewed interest in interaction between the bacterial flora and the mucosal immune system, the collective term for the cells and immune structures located in the GI tract.

The major components of the mucosal immune system are the gut-associated lymphoid tissues (GALT), comprising lymphoid aggregates ([[Peyer's Patches - Anatomy & Physiology|Peyer's patches]] in the jejunum and ileum), individual intra-epithelial lymphocytes (IELs) and the mesenteric lymph nodes.  These lymphoid structures are in close contact with specialised 'follicle-associated' epithelium, a tissue that contains microfold (M) cells capable of sampling antigens from the intestinal lumen.  Many other cell types, including nuerones and the enterocytes themselves are able to contribute to immune responses through the production of cytokines and chemokines.  The B cells of the Peyers patches differentiate to produce antibodies of mainly the [[IgA]] isotype which is then transported into the intestinal lumen by a specific transporter.  This antibody is thought to control bacterial growth in the GI tract and also to help to maintain tolerance to benign antigens by complexing with them and reducing their local availability, a phenomenon called '''immune exclusion'''.

The major components of the mucosal immune system are the gut-associated lymphoid tissues (GALT), comprising lymphoid aggregates ([[Peyer's Patches - Anatomy & Physiology|Peyer's patches]] in the jejunum and ileum), individual intra-epithelial lymphocytes (IELs) and the mesenteric lymph nodes.  These lymphoid structures are in close contact with specialised 'follicle-associated' epithelium, a tissue that contains microfold (M) cells capable of sampling antigens from the intestinal lumen.  Many other cell types, including neurones and the enterocytes themselves are able to contribute to immune responses through the production of cytokines and chemokines.  The B cells of the Peyers patches differentiate to produce antibodies of mainly the [[IgA]] isotype which is then transported into the intestinal lumen by a specific transporter.  This antibody is thought to control bacterial growth in the GI tract and also to help to maintain tolerance to benign antigens by complexing with them and reducing their local availability, a phenomenon called '''immune exclusion'''.

The mucosal immune system of the host and the enteric bacterial flora interact constantly in the gastro-intestinal (GI) tract.  The host must remain tolerant of the enteric flora but must still be able to recognise and respond to potentially pathogenic organisms.  These apparently contradictory tasks are resolved by the ability of the immune system to [[Immune Tolerance - WikiBlood|'tolerate']] certain antigens if these are presented to macrophages and dendritic cells in an appropriate manner.  The major factors that enforce tolerance are immunosuppressive [[Cytokines - WikiBlood|cytokines]] (particularly interleukin 10 and transforming growth factor beta) and immunoregulatory clades of T lymphocytes, although the exact mechanisms by which tolerance is actually achieved are the subject of much research and debate.  '''Most of the recent theories regarding ARD suggest that it results from alterations in the interaction between the mucosal immune system and the enteric flora, particularly a loss of immune tolerance to commensal bacteria.'''

The mucosal immune system of the host and the enteric bacterial flora interact constantly in the gastro-intestinal (GI) tract.  The host must remain tolerant of the enteric flora but must still be able to recognise and respond to potentially pathogenic organisms.  These apparently contradictory tasks are resolved by the ability of the immune system to [[Immune Tolerance - WikiBlood|'tolerate']] certain antigens if these are presented to macrophages and dendritic cells in an appropriate manner.  The major factors that enforce tolerance are immunosuppressive [[Cytokines - WikiBlood|cytokines]] (particularly interleukin 10 and transforming growth factor beta) and immunoregulatory clades of T lymphocytes, although the exact mechanisms by which tolerance is actually achieved are the subject of much research and debate.  '''Most of the recent theories regarding ARD suggest that it results from alterations in the interaction between the mucosal immune system and the enteric flora, particularly a loss of immune tolerance to commensal bacteria.'''