Ama, Microbiome and Leaky Gut:An Evidence based Correlation

Manjusha Vinjamury MD (Ayurveda), MAOM, FAIHM, L.Ac

Presentation Outline

• Introduction: Agni and Ama

• Ama Determination Worksheet

• Correlation between Ama and Leaky gut

• Microbiome and Leaky Gut

• Leaky gut and Inflammation

• Summary and Conclusion

Significance of Agni

“When Agni functions well, one can live healthy and long life; deranged agni can give birth to multiple ailments and diminished agni is indicative of death. Therefore Agni is the root cause of health and disease” - Charaka (Chikista 15:1-2)

Agni and Ama

Agni – Biological fire

• Digests food

• Nourishes body

• Generates energy, enthusiasm

• Governs Ojas, Tejas, Prana

• Renders health and longevity

Ama – Toxic substance

• Undigested food

• Causes obstruction in channels

• Creates lethargy and inertia

• Reduces Ojas, Tejas and prana

• Cause of inflammation and most of the ailments

Common Causes of Ama

• Result of Poor, imbalanced or deranged Agni

• Consumption of heavy, damp, cold, incompatible food

• Irregular dietary habits

• Overeating/excessive fasting

• Lack of exercise

• Suppression of natural urges

• Excessive stress

• Chronic illness

• Intake of Agni weakening drugs like antibiotics/NSAIDS

Pathogenesis of Ama formation

Etiological factors

• Dosha aggravation

Agni mandya

• Poor digestion

Ama(undigested

food)

• Thin biofilm in the gut

Affects Grahani

• Affects Intestinal flora

Spreads through

Srotas (es) (Sama rasa)

• Leaky gut

Effects of Ama on Gut and Body

Gut related symptoms• Indigestion

• Nausea

• Vomiting

• Acid reflux

• Bad breath

• Foul smelling stools

• Poor appetite

• Heart burn

• Loose bowels

• Incomplete evacuation

Other symptoms• Lethargy

• Somnolence

• Dullness

• Lack of enthusiasm

• Fatigue

• Low energy

• Joint pain

• Heaviness of head

• Heaviness of body

Ama Determination Worksheet

1. I have the inability to taste food Yes No

2. I experience sudden fatigue Yes No

3. I feel that my body is heavy Yes No

4. I have pain Yes No

5. I experience abdominal discomfort after eating Yes No

6. I am lethargic and lack motivation Yes No

7. I experience indigestion Yes No

8. I experience constipation Yes No

9. My tongue has a sticky white coat on it Yes No

10. My tongue coat comes back quickly even after I brush it Yes No

11. My stools have a strong odor Yes No

Ama and its effects on Dhatus

Fever

OjasDeficiency

CVD

FMS

Obesity

RA

Neuroinflammation

Fertilityissues

Disorders caused by AmaWhen Ama is localized in Digestive tract (annavaha srotas)

• Indigestion

• Diarrhea

• Constipation

• Nausea/Vomiting

• Acidity

• Abdominal colic

• Anorexia

• IBD• IBS• SIBO

When Ama spreads over through Leaky guts - Systemic (Dhatugata – in tissues)

• Fever

• Cough

• Headache

• Vertigo

• Rheumatoid arthritis

• Fibromyalgia

• Sinusitis

• Diabetes

• Cardiovascular diseases

• Neurological disorders

• Psychological disorders

Grahani Roga

Poor dietary habits, exposure to extreme environment, suppression of urges, poor lifestyle

Agni mandya, indigestion and Ama production Eventually leads to Grahani Roga

Creates structural weakness along with functional pathogenesis - slow and poor digestion, loose, undigested stools, constipation, loss of appetite, nausea, burping, vomiting, acid reflux, stomach cramps Can cause

Systemic Diseases

Grahani and Leaky gut

Chronic indigestion Ama Grahani roga

(Mandagni) (undigested food) (structural damage)

Microbial dysbiosis Gut toxins Leaky gut

(Reduced diversity) (endotoxins) (increased permeability)

Gut Microbiome

• Large number of microorganisms present in gut – bacteria, virus, fungi, protozoa- which regulate and support gut function

• Symbiosis assures health and dysbiosis promotes inflammation and diseases

• Microbial enzymes contribute to bile acid metabolism

• Can be compared to Agni function

Leaky gut?

• Increased intestinal permeability is Leaky Gut

• Antigens, bacteria, toxins and virus enter host through the blood stream because of this increased permeability

• Causes Systemic Inflammation

Leaky Gut and Systemic Inflammation

Gut Toxins: Lipo-polysacchrides (released by dysbiosis of gram negative bacteria), Undigested food, Food additives, Gluten from wheat, barley, etc

Release of zonulin

Loosen the tight cell junctions

Loss of gut permeability control: Gut inflammation

Systemic inflammation

Leaky Gut As a Danger Signal

for Autoimmune

Diseases

• The intestinal epithelial lining, together with factors secreted from it, forms a barrier that separates the host from the environment. In pathologic conditions, the permeability of the epithelial lining may be compromised allowing the passage of toxins, antigens, and bacteria in the lumen to enter the blood stream creating a “leaky gut.”

• In individuals with a genetic predisposition, a leaky gut may allow environmental factors to enter the body and trigger the initiation and development of autoimmune disease. Growing evidence shows that the gut microbiota is important in supporting the epithelial barrier and therefore plays a key role in the regulation of environmental factors that enter the body.

• Several recent reports have shown that probiotics can reverse the leaky gut by enhancing the production of tight junction proteins; however, additional and longer term studies are still required. Conversely, pathogenic bacteria that can facilitate a leaky gut and induce autoimmune symptoms can be ameliorated with the use of antibiotic treatment. Therefore, it is hypothesized that modulating the gut microbiota can serve as a potential method for regulating intestinal permeability and may help to alter the course of autoimmune diseases in susceptible individuals.

• Qinghui Mu,1 Jay Kirby,1 Christopher M. Reilly,2 and Xin M. Luo1,* Front Immunol. 2017; 8: 598.

All disease begins in the (leaky) gut:

role of zonulin-mediated gut

permeability in the pathogenesis of

some chronic inflammatory

diseases

• Improved hygiene leading to reduced exposure to microorganisms has been implicated as one possible cause for the recent “epidemic” of chronic inflammatory diseases (CIDs) in industrialized countries. That is the essence of the hygiene hypothesis that argues that rising incidence of CIDs may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good, so causing changes in our microbiota.

• Apart from genetic makeup and exposure to environmental triggers, inappropriate increase in intestinal permeability (which may be influenced by the composition of the gut microbiota), a “hyper-belligerent” immune system responsible for the tolerance–immune response balance, and the composition of gut microbiome and its epigenetic influence on the host genomic expression have been identified as three additional elements in causing CIDs.

• During the past decade, a growing number of publications have focused on human genetics, the gut microbiome, and proteomics, suggesting that loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between gut microbiome and our immune system. This cross-talk is highly influential in shaping the host gut immune system function and ultimately shifting genetic predisposition to clinical outcome.

• This observation led to a re-visitation of the possible causes of CIDs epidemics, suggesting a key pathogenic role of gut permeability. Pre-clinical and clinical studies have shown that the zonulin family, a group of proteins modulating gut permeability, is implicated in a variety of CIDs, including autoimmune, infective, metabolic, and tumoral diseases. These data offer novel therapeutic targets for a variety of CIDs in which the zonulin pathway is implicated in their pathogenesis.

• Alessio Fasano, Version 1. F1000Res. 2020; 9: F1000 Faculty Rev-69.

The Link between Gut Dysbiosis and Neuroinflammation in Parkinson's Disease

• Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite its high frequency the etiology is still unclear; several lines of evidence show that an inflammatory process is implicated in the pathogenesis of this disorder; where activation of brain microglia plays a central role in the damage of dopaminergic neurons of the substantia nigra.

• Such inflammation has been attributed to the toxic effect of aggregated α-synuclein; however, evidence also implicates an altered gut microbiota (dysbiosis) through the systemic release of endotoxins such as lipopolysaccharide and other metabolic products. This exposure may be enhanced by increased permeability of the intestinal ("leaky gut") and the blood brain barrier; enhancing the entrance of microbiota-produced substances into the central nervous system. In this manuscript, we explore the evidence from clinical and basic science implicating microglia activation by gut dysbiosis and how this phenomenon may impact in the symptomatology and progression of PD.

• Baizabal-Carvallo JF1, Alonso-Juarez M2. Neuroscience. 2020 Feb 27;432:160-173.

The role of gut microbiota in

mediating obesity and

diabetes mellitus

• OBJECTIVE: This review inspects the relations between the microbiota and the intestinal immune system in the advancement of metabolic illnesses, such as obesity and diabetes mellitus. The role of the microbiota in intestinal immune defense and the control of metabolism are subject to examination.

• MATERIALS AND METHODS: In type 1 diabetes, the adhesion proteins prompt inside the intestinal epithelium prompt a more significant immune response that may result in the destruction of pancreatic β cells by CD8+ T-lymphocytes, as well as increased articulation of interleukin-17, which is associated with autoimmunity. Studies suggest that the beginning of metabolic ailments and certain co-morbidities can be viewed in light of the protection between the gut microbiota and the intestinal immune system. The gut microbiota is analyzed as a key regulator of metabolic ailments. Research demonstrates that obese patients with type 2 diabetes have a certain gut microbiota and that the microbiota is translocated from the gut to the tissues in conjunction with the illness, which instigates inflammation.

• RESULTS: Research in animals and people suggests that a probiotic supplement may regulate the gut microbiota, thereby improving the prognosis for diabetes.

• CONCLUSIONS: The mechanism underlying this phenomenon relates to a decrease in the inflammatory reaction and oxidative stress, as well as a decrease in leaky gut. Such reactions increase insulin sensitivity and reduce autoimmune responses.

• Pitocco D1, Di Leo M, Tartaglione L, De Leva F, Petruzziello C, Saviano A, Pontecorvi A, Ojetti V. Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1548-1562

Summary and Conclusion

Agni and Ama are integral to the diagnosis and treatment of all diseases

There are similarities between Agni and Gut Microbiome and Ama and Dysbiosis

Ama in the gut is attributed to decrease dhatwagni, create srotodushti, and eventually lead to dhatugata rogas (systemic diseases)

Leaky gut is also attributed to systemic diseases due to similar pathogenesis. This has been established by various studies that indicate the relationship of leaky gut and inflammation and other conditions

Questions