In our previous post of Ketogenic therapy and Autism, we had given a brief idea about leaky gut syndrome so today we will discuss this in depth.

KETOGENIC THERAPY AND AUTISM

What is Leaky Gut?

The lining of our intestines are made up of tiny cells that are naturally permeable only to very small molecules in order to absorb vital nutrients. This forms a barrier called the gut blood barrier (GBB). In leaky gut syndrome, these tight junctions loosen, potentially allowing harmful substances like bacteria, toxins and undigested food particles to enter your bloodstream.

Signs and Symptoms of leaky guts:-

1. Chronic diarrhea, constipation, flatulence or bloating
2. Skin rashes and problems such as acne, eczema or rosacea (Whitney P Bowe et al.,2011)
3. High blood sugar levels (Fändriks L1.2017)
4. Arthritis or joint pain (Fasano A1.2012)
5. Excessive fatigue
6. Autoimmune diseases such as rheumatoid arthritis, lupus, celiac disease or Crohn’s disease (Fasano A1.2012)

Causes of leaky gut:-

• Stress has immunologic consequences and thus has a role in these interactions. For example, IL-1 and IL-6 are able to increase cortisol release by the stimulation of hypothalamic pituitary arm of the microbiota gut brain (MGB) axis and stressed or depressed patients often exhibit disturbances  in this axis, resulting in elevated cortisol levels. In addition to the microbiome, the mycobiome participates in modulating cytokine production, with IL-6 (Mello et al.,2003) Thus, cytokines produced in the gut reach the brain via the bloodstream, where they affect immune pathways. Corticotrophin releasing factor (CRF) and its receptors (CRFR1 and CRFR2), play a key role in stress-induced gut permeability dysfunction (Overman et al., 2012; Rodiño- Janeiro et al., 2015; Taché and Million, 2015).
• Food sensitivity and emerging glycotoxins have been linked to inflammation (Wahab, P.J et al., 2001)
• Food and dietary proteins:- some individuals react to food and dietary proteins as pathogenic or antigenic, causing inflammation of the mucosal barrier and cytokine stress.
• Use of antibiotics:-The microbiota-gut is an integral component of the gut–brain neuroendocrine metabolic axis and any disruption that can occur, such as antibiotic use during disease, could upset homeostasis and share an inflammatory component. Antibiotic use, depression and psychiatric comorbidities occurred in irritable bowel disease and have been associated with a systemic inflammation. Inflammatory reactions can also disrupt the blood brain barrier, the so-called leaky brain, leading to increased CSF protein and their translocation. (Maes, M et al., 2008)

Blood brain barrier:–  The diagram below shows the brain-gut-microbiota axis and postulated signaling pathways between the gut microbiota, the intestinal barrier and the brain. A dysfunctional intestinal barrier or “leaky gut” could permit a microbiota-driven proinflammatory state with implications for neuroinflammation. (Kelly et al 2015)

Leaky Gut and Celiac Disease

Leaky gut causes celiac disease, an autoimmine disorder that presents as diarrhea and bloating.  This can also cause chronic inflammation throughout the body resulting in a wide range of conditions, including chronic fatigue syndrome, rheumatoid arthritis, lupus, migraines, multiple sclerosis, and autism (NHS Choices. 26 February 2015; Odenwald, Matthew A et al.,2013 ) As of 2016, there is little evidence to support the hypothesis that leaky gut syndrome directly causes this wide array of diseases. (Quigley EM ,2016).

Brain Disorders and the Microbiota

A dysfunction of the blood brain barrier leading to a ‘leaky brain’ can be linked to various neurological diseases, including autistic spectrum disorder (ASD), dementia, Alzheimer’s disease, depression, and schizophrenia. (Obrenovich, M.E et al.,2014 and Bravo, J.A et al., 2011)

What are the Signs and Symptoms of a Leaky Brain?

How to Find Out If You Have Leaky Gut. (Dr. Jolene Brighten)

Urine Test:

After drinking a carbohydrate solution (lactulose and mannitol) you will need to collect your urine for 6 hours. Urine that contains high amounts of the sugar is considered a positive for leaky gut.

IgG and IgA Food Intolerance Testing:

Food intolerance testing can reveal leaky gut and provide information regarding which foods to avoid to help heal your gut.

Data source:- Kelly et al.,2015

How to treat the leaky gut syndrome:

First seal your intestine with bone broth or for vegetarians a high cruciferous vegetable diet  

PAYA SOUP FOR HEALTHY INTESTINE

Bone Broth, traditionally known as “Paya Soup” is made using leg bones of Goat or Lamb. Paya Soup is the soothing bone broth, which is nutrient-dense, easy to digest, rich in flavor and boosts healing.

Many studies on Paya Soup have shown that glutamine, an amino acid that is the best known compound and  abundant in bone broth, can help repair Leaky Gut.

Bone Broth is also a rich source of Protein named Collagen, which helps to repair the intestinal lining, further strengthening the intestinal junctions,  and may strengthen immunity and improve bone health.

 It is advised to take Paya soup, on alternate day, to maintain Healthy Gut.

Benefits of Bone marrow

• It contains omega-3 fatty acids, vitamin A, calcium, iron, phosphorous, zinc, selenium, magnesium, and much more.

Bone broth:-

• It is rich in collagen heals your gut lining, and can even reduce inflammation.
• Also contains proteins like, glutamine, glycine, and proline.

Method of cooking Paya Soup

-Heat oil in pressure cooker/or open pot. -Add ginger ¼ inch, garlic 4-5 cloves, cook for some time. -Add celery, onion, turmeric ½ tsp, black pepper 4-10 no, cinnamon ½ stick, cardamom 1 pod, bayleaf & salt. -Finally add mutton paaya to it and pressure cook for 6-7 whistles or cook in an open pot for 3-4 hours, strain & serve.

For Vegeterian -Cruciferous vegetable in healing leaking gut:-

Role of Glucosinolate compounds and  Sulforaphane in healing leaky gut:-

Sulforaphane (SFN) is an isothiocyanate. It is derived from glucoraphanin, (Glucoraphanin is a glucosinolate found in broccoli, cauliflower, and mustard). Glucoraphanin is converted to Sulforaphane by the enzyme Myrosinase found in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussels sprouts and kale. (Fahey et al., 2015)

Glucosinolates and myrosinase  are stored in separate cell compartiments. Break down of the cell, e.g. by chewing, cutting or heating, leads to the release of
glucosinolates and myrosinase. Myrosinase causes hydrolytic cleavage of glucosinolates as exemplified for glucoraphanin present in high concentration in broccoli. The resulting compound is isothiocyanate sulforaphane (Ingrid Herr et al.2013)

Other functions of Sulforaphane:-

Inhibits inflammation by reducing damaging reactive oxygen species (ROS) by as much as 73 percent .(Mingzhan Xue et al., 2008).

It is also an immune stimulant. (Kim et al.,2008).

Metabolism:-

Glucosinolate compounds, which are broken down into ICZ (Indolocarbazole) and other by-products during digestion in the stomach. By binding to and activating aryl hydrocarbon receptors (AHR) which are the receptors located on the lining of your gut wall, ICZ plays a vital role in maintaining a well-functioning barrier to prevent particles from escaping from your intestinal tract into your bloodstream. ICZ also helps boost immune function and improve the balance of the microbiome in the gut.

So cruciferous vegetables beneficially influence your immune function in more ways than one.

Effect of cooking on cruciferous vegetables:-

1. Research shows steaming broccoli for three to four minutes will increase the available sulforaphane content by retaining the enzyme myrosinase, which converts glucoraphanin to sulforaphane. Without myrosinase, you cannot get absorb the sulforaphane. (Science Daily April 5, 2005)
2. When a cruciferous vegetable is chopped, myrosinase is activated. So, by chopping the food and waiting about 40 minutes, the sulforaphane will have formed, allowing you to cook the food in excess of the recommended three to four minutes of steaming, or 30-second blanching,without risking sulforaphane loss. As an example, if making broccoli soup, blend the raw broccoli first; wait 40 minutes for the sulforaphane to form, then boil it.
3. Do not exceed the five-minute mark, as you start losing valuable compounds beyond that point. If you opt for boiling, blanch it in boiling water for no more than 20 to 30 seconds, then immerse it in cold water to stop the cooking process.
4. Eat cruciferous veggies with mustard seed/powder/sauce which is myrosinase-rich food. Especially if you eat the broccoli raw, or use frozen broccoli then adding a myrosinase-rich food is particularly important (Dosz EB et al., 2013)

STEP WISE METHOD OF COOKING CRUCIFEROUS VEGETABLES (CAULIFLOWER, BROCOLLI AND CABBAGE)

1) Cut, chop & clean the cruciferous vegetable.

2) Keep it uncovered for 40 mins in open air.

3) Blanch it in boiling water for 2 mins (Blanching means water is already boiling you add your vegetable and keep it immersed for 2mins) 

4) Remove the vegetable from blanching water and wash it under cold running water to stop the process of blanching.

5) Finally add the cruciferous vegetable to your soup preparation and give it a mix, switch off the gas within 1min. 

Remember: Do not exceed the total cooking time beyond 4 mins. 

FOODS TO HEAL A LEAKY GUT:

Source:-https://www.healthline.com/nutrition/leaky-gut-diet#foods-to-eat

VEGETABLES & FRUITS	VEGETABLES Arugula, Spinach, Squash, Zucchini. Broccoli, Brussels Sprouts, Cabbage, Carrot, Brinjal, Beetroot, Kale	FRUITS Strawberry, Pineapple, Oranges, Mandarin, Sweet Lime, Raspberries, Papaya Grapes, Blueberries, Kiwi
FERMENTED VEGETABLES	Kimchi, sauerkraut, tempeh and miso
SPROUTED SEEDS & NUTS	Chia seeds, flax seeds, sunflower seeds Raw nuts including peanuts, almonds & nut based milks
CEREALS	Buckwheat, amaranth, rice (brown and white), sorghum, and gluten-free oats.
FISH & MEAT	Salmon, tuna, herring, mackerel Lean cuts of chicken, beef, lamb, turkey and eggs
DAIRY PRODUCTS	Yogurt, Greek yogurt and buttermilk
BEVERAGES	Bone broth, Tea, Water
SPICES & HERBS	All herbs and spices.
SUGAR-FREE SWEETENER	Stevia extract pellets or liquid drops

FOODS TO AVOID FOR LEAKY GUT SYNDROME 

WHEAT BASED PRODUCTS	Bread, pasta, cereals, wheat flour, couscous
GLUTEN CONTAINING GRAINS	Barley, rye, bulgur
PROCESSED MEATS	Cold cuts, deli meats, bacon, hot dogs
BAKED GOODS	Cakes, muffins, cookies, pies, pastries and pizza
PROCESSED FOODS	Crackers, muesli bars, popcorn, pretzels, potato chips
DAIRY PRODUCTS	Milk, cheeses and ice cream
BEVERAGES	Alcohol, carbonated beverages
ARTIFICIAL SWEETENERS	Aspartame, sucralose, Saccharin

References:-

1. Leaky gut syndrome”. NHS Choices. 26 February 2015. Retrieved 15 August 2016.
2. Whitney P Bowe et al. Acne vulgaris, probiotics and the gut-brain-skin axis – back to the future? Gut Pathog. 2011; 3: 1.
3. Fändriks L1. Roles of the gut in the metabolic syndrome: an overview. J Intern Med. 2017 Apr;281(4):319-336.
4. Fasano A1. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8.
5. Odenwald, Matthew A.; Turner, Jerrold R. (2013). “Intestinal Permeability Defects: Is It Time to Treat?”. Clinical Gastroenterology and Hepatology. 11 (9): 1075–83. 
6. Quigley EM (2016) Leaky gut – concept or clinical entity?”. Curr Opin Gastroenterol (Review). 32 (2): 74–9.
7. Mello, A.A.; Mello, M.F.; Carpenter, L.L.; Price, L.H. Update on stress and depression: The role of the hypothalamic-pituitary-adrenal (HPA) axis. Rev. Bras. Psiquiatr. 2003, 25, 231–238.
8. Overman, E.L., Rivier,J.E.,andMoeser,A.J.(2012). CRFinducesintestinal epithelial barrierinjuryviathereleaseofmastcellproteasesandTNF-alpha. PLoS ONE 7:e39935. doi:10.1371/journal.pone.0039935
9. Rodiño-Janeiro,B.K.,Alonso-Cotoner,C.,Pigrau,M.,Lobo,B.,Vicario,M.,and Santos,J.(2015).Roleofcorticotropin-releasingfactoringastrointestinal permeability. J. Neurogastroenterol.Motil. 21, 33–50.
10. Taché,Y.,andMillion,M.(2015).Roleofcorticotropin-releasingfactor signaling instress-relatedalterationsofcolonicmotilityandhyperalgesia. J. Neurogastroenterol.Motil. 21, 8–24.
11. Wahab, P.J.; Crusius, J.B.; Meijer, J.W.; Mulder, C.J. Gluten challenge in borderline gluten-sensitive enteropathy. Am. J. Gastroenterol. 2001, 96, 1464–1469
12. Maes, M.; Kubera, M.; Leunis, J. The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol. Lett. 2008, 29, 117–124
13. Obrenovich, M.E.; Shola, D.; Schroedel, K.; Agahari, A.; Lonsdale, D. The role of trace elements, thiamine and transketolase in autism and autistic spectrum disorder. Front. Biosci. 2014.
14. Bravo, J.A.; Forsythe, P.; Chew, M.V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA 2011, 108, 16050–16055.
15. John R. Kelly et al. Breaking Down the Barriers: The Gut Microbiome, Intestinal Permeability and Stress-related Psychiatric Disorders. October 2015 ,Volume 9,Article 392.
16. Fahey JW, Holtzclaw WD, Wehage SL, Wade KL, Stephenson KK, Talalay P. Sulforaphane bioavailability from glucoraphanin-rich broccoli: control by active endogenous myrosinase. PloS One. 2015;10:e0140963
17. Mingzhan Xue et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 2008 Aug.
18. Kim et al. Nrf2 activation by sulforaphane restores the age-related decline of Th1 immunity: Role of dendritic cells. J Allergy Clin Immunol. 2008 May ; 121(5): 1255–1261.
19. Science Daily April 5, 2005
20. Dosz EB, Jeffery EH. Modifying the processing and handling of frozen broccoli for increased sulforaphane formation. J Food Sci. 2013 Sep;78(9):H1459-63.
21. https://www.healthline.com/nutrition/leaky-gut-diet#foods-to-eat