MUTLU 2011:
"...Many of the adverse health consequences of particulate matter (PM) are thought to be caused by the ability of PM to induce cellular oxidative stress, which activates signalling pathways that contribute to cytokine release and barrier dysfunction (Nel 2005)...
...Exposure to high doses of PM cause oxidant dependent gastrointestinal tract (GI) epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo. These PM induced changes may be responsible for exascerbations of inflammatory disorders of the gut...
...An important limitation of our study is the dose of PM that we employed for our in vivo experiments...6-8 times higher than a US adult will be exposed in even the most polluted city...
...the total dose of PM to which the gut is exposed is likely at least as large as that seen by the lung. However, the more rapid transit time of the mucous layer over the gut compared with the lung mucosa may decrease the concentration of PM to which the gut is exposed at any given time..."

SPC 8b)

MERCK 1999:
"...Crohn's disease and ulcerative colitis are characterized by chronic inflammation of various sites in the GI tract. Both cause diarrhea which may be profuse and bloody...evidence suggests that a genetic predisposition leads to an unregulated intestinal immune response to an environmental, dietary, or infectious agent..."

SPC 8c)

ANANTHAKRISHNAN 2011:
"... Inflammatory bowel diseases (IBDs) refer to two chronic intestinal inflammatory disorders, Crohn's disease (CD) and ulcerative colitis (UC), which typically have their onset during young adulthood (Abraham 2009). Together, these affect an estimated 1.4 million people in the United States (Abraham 2009) and account for over $6 billion USD in direct health care costs (Kappelman 2008). This past few decades have seen a striking increase in the incidence of IBD (Loftus 2000, 1998) and the number of IBD-related hospitalizations (Bewtra 2007)...
...Known genetic variations account for less than 25% of IBD risk (Abraham 2009)...
...The incidence of IBD has increased relatively rapidly over the past few decades, which cannot be explained through genetic mechanisms (Lakatos 2009, Koloski 2008, Danese 2004, Loftus 2000, 1998). Moreover, this increase has been particularly striking in several developing countries where IBD was once considered rare (Thia 2008)...
...Oikonen 2003 examined the relationship between ambient air quality and the occurrence of multiple sclerosis relapses and found that the odds of relapse were 4-fold higher during months with the highest quartile of airborne PM. The authors concluded that poor ambient air quality may increase susceptibility to transmissible infections or enhance already existing peripheral inflammation, triggering a disease flare. Thus, it is possible that there exists a similar systemic inflammatory response to air pollution exposure that may play a role in triggering IBD flares and consequently IBD-related hospitalizations...
...county-level criteria air pollutant emissions directly correlated with the rate of IBD hospitalizations in Wisconsin...while the correlation between air pollution density and IBD hospitalizations was significant, the strength of the correlation was only moderate..."

SPC 8d)

KAPLAN 2009:
"...A pro-inflammatory response occurs with appendicitis that includes expression of cytokines...
...Animals fed diesel particles experienced oxidative damage in colonic mucosa (Dybdal 2003)...and exposure to air pollutants, either through inhalation or ingestion, may induce inflammatory responses that are also evident in appendicitis. Alternatively, exposure to diesel exhaust has been shown to increase susceptibility to bacterial (Siguad 2007) and viral (Ciencewicki 2007) pulmonary infections through impairment of microbrial defense (Gowdy 2008). If air pollution effects gastrointestinal immunity, exposure to pollutants may increase the risk of bacterial invasion resulting in appendicitis...
...Our findings indicate that some cases of appendicitis may be triggered by short term exposure to air pollution...the effect size of the risk estimates were modest..."

SPC 8e)

CALDERON-GARCIDUENAS 2008:
"...We know that systemic cytokines could effect the CNS via sensory nerves such as the vagus. This could be a consequence of exposure to air pollutants, because IL-1beta is recognized by chemosensory receptors located in vagal paraganglia in the vagus nerve at several levels, including the cervical, thoracic, and abdominal regions (Elmquist 1997)...
...the presence of PM in Kupffer cells - the liver resident macrophages (Uyama 2004, Wake 1989) responsible for the clearance of foreign material arriving from the circulation and the gut (Wake 1989) - is a very interesting finding, given that the liver and digestive tract are preferred sites for extrapulmonary translocation of ultrafine particles in humans and rats (Oberdorster 2002)...
...in MC residents with a disrupted and ineffective nasal barrier, major concentrations of PM would be swallowed and thus enter the digestive system, the liver pathway, and the right vagus...the brain stem is taking part in the inflammatory process, either through local pathways or systemic inflammation or both, and the brain stem participation likely also depends on the PM entry pathways (i.e., digestive and lower respiratory systems)..."

SPC 8f)

BLOCK 2012:
"...It is known that PM particulates that are too large to enter the lungs are quickly cleared by swallowing (Mutlu 2011). Likewise, clearance of particles that deposit in the deep lung eventually occurs via the mucociliary escalator and so, gastrointestinal tract exposure cannot be discounted. The sensory afferents of the dorsal vagus nerve located in the gut communicate directly with brainstem neurons. It is interesting to note that abnormalities in olfaction-vagal-brainstem routes (gastric systems secondary to swallowing of nasal secretions in saliva) have been studied as the early pathologies of Parkinson's neurodegeneration (Jang 2009, Hawkes 2007)..."

SPC 8g)

EMCH 2000:

"...it is likely TNF alpha inhibits gastric motility by directly affecting the sensitivity of gastric vagal control circuitry in the medulla. This vago-vagal reflex circuit is outside the blood brain barrier and therefore is readily accessible to large circulating peptides. Additionally TNF alpha increases vascular-brain permeability and TNF alpha may gain access to the brain through a specific transport system..."

This inhibition of gastric motility or stasis is perceived as queasiness or nausea.

SPC 8h)

GI total dose of PM may be large as that of the lung, however the more rapid transit time of intestinal mucosa and the potential diluting and ameliorating effects of dietary substrate may decrease exposure of the GI epithelial layer

(Mutlu 2011, Priebe 2010, Malik 2007, Prior 2003, Slavin 2003, Drewnowski 2000, Olson 1995, Groff 1990, Cummings 1987, Chako 1969, Cook 1969).

Significant, but modest associations have been found between ambient combustion aerosol (ACA) exposure and hospitalizations for inflammatory bowel disease (Ananthakrishnan 2011) and appendicitis (Kaplan 2009).

Exposure to urban PM - at doses at least 6-8 times higher than environmentally relevant are demonstrated to cause oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo (Mutlu 2011).

Taken together, it appears that GI symptoms are more likely to occur as a result of PM exposure in MCS and ME/CFS when combined with a low fiber diet which slows transit time and leaves little large intestinal (colonic) substrate for bulk, dilution, and potential metabolic detoxification activity of bacterial flora.

PM or other chemical inflammatory effects directly on vagal circuitry - with GI results such as stasis or nausea (Emch 2000) - may be less influenced by dietary factors.

SPC 8i)

Gastrointestinal involvement in MCS and ME/CFS - such as gastric stasis and nausea - should not be considered as possibly due to communication of brain stem neurons with sensory afferents of the vagus nerve in the GI tract in response to systemic inflammatory mediators or direct PM exposure - viscero sensory pathways originating in the nucleus of the solitary tract and ventrolateral medulla - gastric vagal control circuitry (Block 2012, Calderon-Garciduenas 2008, Emch 2000).

SPC 8j)

Not to be confused with reactivity to air pollution -

the action of excessive dietary fructose on bacterial flora (10% of US calories and often exceeding 20% among America's youth) - in the Western dietary context - and even if not in a weight gain situation - may result in:

lower scores on tight junction protein measures - impacts on intestinal wall integrity - alteration or bloom of bacteria - increased microbrial translocation (MT) from the gastrointestinal tract and endotoxemia - higher plasma endotoxin concentrations (inflammatory cell wall components of gram negative bacteria), soluble CD-14 LPS (lipopolysaccharide endotoxin) receptors, and LPS binding protein-1 (LBP-1),

large elevations in c-reactive protein and liver enzymes - alanine transferase, alkaline phosphatase, and y-glutamyl transpeptidase - LPS overwhelming local and innate immune mechanisms reaching kupffer (liver macrophages) and non immune liver cells producing periportal inflammatory infiltrates - liver damage -

which if accompanied by extra calories leads to Hepatic Steatosis (HS) - today's epidemic of nonalcoholic fatty liver disease (NAFLD) afflicting nearly 1/3 of the US population -

fructose participation in lipogenesis - unlike glucose, not involving insulin - fructose 90% uptake by the liver promoting insulin resistance adversely effecting glucose metabolism disposing to the development of type 2 diabetes and cardiovascular disease (Kavanagh 2013, Hellerstein 2012).

8k)

Another area of potential gastrointestinal confusion concerns dietary fiber composition.

Studying small intestinal biopsies of South India adults, Baker 1963 found villi were no longer finger-like as present in human fetuses - but instead leaf-like with changes maximal at the duodenum and upper jejunum and contrasting with Western man where similar distortions in villus structure had only been associated with pathological states.

Cook 1969, in biopsy of African jejunal mucosa found villus structure both leaf shaped with normal d-Xylose absorption (grade 2) and leaf shaped coalescing to form short ridges with abnormal d-Xylose absorption (grade 3).

Owen 1977 compared biopsies of San Francisco vegetarians with those on American mixed diets and reported vegetarians showed fusion of the tips, branching, and broadening - but not shortening of the villi - with more plasma cells in the lamina propria and lymphocytes in the villus epithelium compared to the mixed diet group.

Tasman-Jones 1978 confirmed villus alteration in rats and implicated pectin as a likely culprit - number of villi in the jejunal and ilead small intestine:

fiber free 1769 and 3174

fiber free + cellulose 1789 and 3467

fiber free + pectin 1548 and 2802

Despite other unhealthful aspects, the finger-like villi of the newborn remain so in adults consuming traditional Western diets which do not emphasize unrefined plant foods (Owen 1977, Baker 1963).

Africans whose diets predominate in plant foods and vegetarians studied in San Francisco have a broadening of the villus structure with a reduced number of villi (Owen 1977, Cook 1969) thought to be caused by viscous fiber - especially pectin (Tasman-Jones 1986, 1978, Baker 1963).

It appears that hemicellulose of brown rice and cellulose found in both rice and vegetables do not cause broadened villi - which is a loss of absorptive surface (Tasman-Jones 1986,1978).

Pectin has been associated with cell swelling, loss of microvilli, and hemorrhage on the surface of the jejunum. In addition, 7 subjects fed a diet with 20 grams of apple pectin for 4 weeks not only has delayed gastric emptying during that period but also were found to take twice as long to empty the stomach of a pectin free meal following a 16 hour overnight fast (Schwartz 1982).

Fruit, oats, barley, and legumes contribute to a large amount of pectin - and tubers such as carrots, turnips, and potatoes are also suspect. Other vegetables such as cauliflower and brussels sprouts are noted to bring about undesirable digestive symptoms - though perhaps at least partly due to fructose content.These foods also lack the nutrient density of green vegetables.

The viscous fibers in legumes, barley, and oats have been portrayed as the good guys in glycemic index (Jakobsen 2010, , Liu 2000) - but they may be involved with villus structure alteration and causing undesirable digestive symptoms and interference. This area of concern seems to have received little attention - adverse effects due to indiscriminant consumption of fruit, vegetables and grains.

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MCS Consensus IV

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