Immunology suggests the appendix has a use after all

The appendix has long had a reputation as a redundant organ with no real function. You might want to hang on to it if you can, however.

appendix

Doctors often remove it even in mild cases of appendicitis to prevent future infection and rupture, which may not always be necessary. New research on the way innate lymphoid cells (ILCs) protect against infection in people with compromised immune systems may redeem this misunderstood organ.

“Our study was to investigate the ILCs in the gut [of mice] and how they might contribute to the function and protection of the gut,” says Gabrielle Belz, of Melbourne’s Walter and Eliza Hall Institute of Medical Research. “At the same time, we were interested to know how different immune cells impacted the different parts of the gut.”

ILCs can be found “underlying all the body’s surfaces, including the skin, the lungs, the gut, and the reproductive tract, and play a very important and broad role in protecting the body from infections and responses to environmental insults,” says Belz.

appendixcomicBelz’s team worked in collaboration with a team headed by Eric Vivier at the Centre d’Immunologie de Marseille-Luminy, France. Together, they set out to explore how ILC3s (one group of ILCs) function during and after a gut infection – particularly how they altered immune protection.

The study, published in Nature Immunology, found that in mice, gut infections begin in the cecum, a small pouch that is considered to be the beginning of the large intestine, and which contains a large patch of ILC3s near its tip. The team infected mice with the murine pathogen Citrobacter rodentium, which establishes first in the cecum. Then they removed the ILC3s, which caused shrinkage of the cecum and inflammation in the colon. Moreover, they uncovered a “layered contribution” of each of the different types of immune cells in the cecum.

“Thus, surprisingly, altering the balance of immune cells significantly affected what was happening in the cecum, suggesting that a similar effect might occur in humans in the appendix,” Belz says. “This highlights that simply disposing of this organ may not always be in our best interests.”

While the appendix is not required for digestive functions in humans, Belz says, “It does house symbiotic bacteria proposed by Randal Bollinger and Bill Parker at Duke University to be important for overall gut health, but particularly when we get a gut infection resulting in diarrhoea.”

Infections of this kind clear the gut not only of fluids and nutrients but also good bacteria. Their research suggests that those ILCs housed in the appendix may be there as a reserve to repopulate the gut with good bacteria after a gut infection.

ILCs are hardier than other immune cells, and thus vital to fighting bacterial infections in people with compromised immune systems, such as those in cancer treatment; they are some of the few immune cells that can survive chemotherapy.

Belz says that changing the way the appendix is regarded (from vestigial to integral) may also help prevent unnecessary appendix operations. In non-emergency cases of appendicitis, for instance, non-surgical treatments such as antibiotics “can be used to endeavor to calm the inflammation down in the cecum and appendix,” she says. And a healthy appendix may be helping to keep your gut microbiome balanced. Belz has conducted prior research that shows that diet, particularly leafy green and cruciferous vegetables, may help produce ILCs as well.

More study can also help understand how ILCs play a role in allergic diseases such as asthma, inflammatory bowel disease, and psoriasis. At the very least, Belz says, “It seems likely that [the appendix] is an integral part of the immune system.”

Reference:

Rankin, C.L., et al., Complementarity and redundancy of IL-22-producing innate lymphoid cells. Nature Immunology, 2016. 17: p. 179–186.

Non-Coeliac Gluten Sensitivity

He even went through periods where he could not walk properly – CK

non-celiac gluten sensitivityI’ve been told personally that a little gluten never hurt anyone. Clinical experience proves otherwise. The combination of misunderstanding, ignorance and rise in everything pervasively gluten-free has made the topic seem like a modern day fad. Unfortunately, this phenomenon affects those most for whom gluten sensitivity is a real, clinical issue.

It is now becoming clear that, besides those with coeliac disease or wheat allergy, there are people with gluten sensitivity in whom neither allergic nor autoimmune mechanisms can be identified1. It has been estimated that for every person with coeliac disease there should be at least 6 or 7 people with non-coeliac gluten sensitivity (NCGS)1. In 2011 in London, a panel of 15 experts announced a new classification of gluten-related disorders (see yellow boxes below) that was then published in February 20122. The Second Expert Meeting on gluten sensitivity that was held in Munich in 2012, decided to change the name of gluten sensitivity to non-coeliac gluten sensitivity in order to avoid confusion with coeliac disease3.

The challenge with diagnosing NCGS is that currently there are no laboratory biomarkers specific for gluten sensitivity and the diagnosis is based mainly on exclusion criteria: elimination of gluten-containing foods from the diet and monitoring symptoms. Occasionally people will say they have attempted a gluten-free diet, yet symptoms persist. The problem with this is, firstly, foodstuffs nowadays are a complex minefield of chemicals and people may exhibit cross-reactivity with other wheat-based molecules and, secondly, the person may not have been strict enough with the diet or persisted long enough to heal the gut. Being completely gluten-free is incredibly challenging and often too difficult, so alternative diagnoses to gluten sensitivity are sought and the underlying issue is missed.

Many people that are intolerant of gluten are also intolerant of other proteins found in foods like dairy, eggs, and even coffee and milk protein. Critics of the gluten-free diet argue that people with irritable bowel syndrome (IBS) are not sensitive to gluten, but instead are reacting to a group of poorly absorbed carbohydrates called FODMAPs4 (figure below). From a practical perspective, wheat and many other gluten-containing grains are FODMAPs and should be avoided by people with gluten sensitivity anyway.

IBS FODMAPS

Coeliac disease is easier to diagnose than NCGS. Most doctors today know how to screen for coeliac disease. They will typically test for antibodies to alpha gliadin, transglutaminase-2, deamidated gliadin, and endomysium, and if positive do a biopsy to determine if tissue damage is present. However, we now know that people can (and do) react to several other components of wheat above and beyond alpha gliadin, the component that is implicated in coeliac disease. These include other epitopes of gliadin (beta, gamma, omega), glutenin, wheat germ agglutinin (WGA), gluteomorphin, and deamidated gliadin5,6.

The bottom line is standard blood tests by general practitioners are not comprehensive enough. The person may be reacting to deamidated gliadin, glutenin, gluteomorphin, and either transglutaminase-3 or -6, but not reacting to alpha gliadin or transglutaminase-2 (the antibodies used to screen for coeliac disease by most doctors). They will remain undiagnosed and continue to eat gluten for the rest of their lives, suffering symptoms and putting themselves at serious risk for autoimmune diseases.

The typical presentation of NCGS is a combination of IBS and systemic manifestations like headache, joint and muscle pain, muscle contractions, leg or arm numbness, chronic fatigue, “brain fog”, body mass loss and anaemia. Symptoms can also include behavioural disturbances such as changes in attention or depression2 (Table of NCGS symptoms).

IBS can include abdominal pain, nausea, bloating, flatulence, diarrhoea or constipation. People with IBS who respond well to a gluten-free diet can suffer from one of the three diseases: coeliac disease, wheat allergy or NCGS, where NCGS is the most likely option (figure above). In children, NCGS manifests with intestinal symptoms – abdominal pain and chronic diarrhoea – but also symptoms beyond the gut.

Extragastrointestinal manifestations seem to be less frequent but the most common is chronic tiredness. When a person with NCGS consumes wheat or other gluten-containing foods, he or she may not always experience the classic digestive symptoms associated with gut because they do not produce antibodies to transglutaminase-2 (which is mostly expressed in the gut). Instead, the intolerance of wheat may manifest in skin conditions like eczema or psoriasis; and in neurological or brain-related conditions like depression, peripheral neuropathy (pain, numbness, burning, tingling), ataxia (difficulty walking) or ADHD7. Current evidence suggests that neurological manifestations are immune-mediated and that there is cross-reactivity between immune cells, nerve cells and gluten proteins.

Gluten sensitivity is a common disorder that manifests in diverse ways, making it a difficult condition to diagnose. Many people who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms7

Read more

Nausea, bloating and constipation

Nausea, bloating and constipation are common and often non-specific symptoms.

Patients can present with one or all three symptoms and not even realise they are constipated. Surprisingly, 50 percent of people who complain of nausea, bloating or constipation have normal bowel movements1.

normal colon chiropractic

In health, the right colon usually functions as a reservoir, mixing contents, while the left colon functions as a conduit. In constipated people, measurement of colonic transit may reveal segmental (right-sided, left-sided or rectosigmoid) delays in colonic movement2.

The term “slow transit constipation” refers to a clinical syndrome attributable to ineffective colonic propulsion3. Sometimes patients complain of constipation but there is no underlying systemic disorder or pelvic floor dysfunction that explains the symptoms. There will be no pathological finding on imaging either. The person may complain of other symptoms such as nausea, bloating, painful or irregular periods, urinary hesitancy, cold hands or fainting. These are called “extragastrointestinal” symptoms.

colonic inertia B&W chiropractic

Potential causes of this subtle problem can be wide and varied, such as medications, pain killers, allergies to certain foods, candida, stress, anxiety or dysfunction of the autonomic nervous system. However, the underlying mechanism of slow transit constipation is reduced colonic contractile activity, which needs to be kick started again. This is called “colonic inertia”. The image above shows normal colonic contractions following a 1,000 kcal meal.

Symptoms such as abdominal bloating, discomfort and nausea are attributed to delayed colonic transit with “back up” of contents and perhaps bowel distention3

Read more


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