Koshtha

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The word ‘koshtha’ literally means enclosure or gut. Over the past decade, the concept of gut has revolutionized the health and wellness industry. The state of gut and its flora in every aspect of life, their impact on health and disease, interaction with the other parts of the body and external stimuli have been areas of interest in current research. Ayurveda has appreciated the role of gut in all the domains; conceptual, diagnostical and therapeutical. The multidimensional term ‘Koshtha’ has been used to denote the gut in Ayurveda. It has been comprehended as an organ, a collection of organs or a system, a channel, a disease pathway, and a therapeutic target. In the present article, the contributions of Ayurveda in each of these realms have been explored.

Contributors
Section/Chapter/topic Sharira / Koshtha (The concept of gut in Ayurveda)
Author Karthik K.P.1
Reviewer Basisht G.2
Editor Deole Y.S.3
Affiliations

1 Department of Kaumarabhritya, A.I.I.A., New Delhi, India

2 Rheumatologist, Orlando, Florida, U.S.A.

3 Department of Kayachikitsa, G.J. Patel Institute of Ayurvedic Studies and Research, Anand, India
Correspondence email kpkarthik131@gmail.com, carakasamhita@gmail.com
Publisher Charak Samhita Research, Training and Development Centre, I.T.R.A., Jamnagar, India
Date of first publication: May 08, 2022
DOI 10.47468/CSNE.2022.e01.s09.097

The anatomical and physiological perspective

Anatomy of koshtha

The meaning of the word ‘Koshtha’ is ‘enclosure’. In Ayurveda, koshtha denotes the following anatomical ranges:

  • Stomach to large intestines (amashaya to pakvashaya).[A.Hr.Sutra Sthana 12/46][1]
  • Mouth to rectum (asya to payu).[Gayadasa commentary on Su.Sa.Nidana Sthana 7/6][2]
  • Site (sthana) of collection of undigested food (ama), digestive fire (agni), digested food (pakva), urine (mutra), blood (rakta), and the organs, heart (hridaya), caecum (unduka), and lungs (phupphusa).[Su.Sa.Chikitsa Sthana 2/12-13][2]
  • The term koshtha is also used to refer to duodenum (grahani), which is the pivot of digestion.[Su.Sa.Nidana Sthana 7/6][2]
  • It is considered as a separate pathological terrain (rogamarga), serving as a stratum for its own unique set of diseases.

Fifteen organs have been enunciated as parts of koshtha: umbilicus (nabhi), heart (hridaya), pancreas (kloma), liver (yakrit), spleen (pleeha), kidneys (vrkkau), bladder (vasti), sigmoid colon (purishadhara), stomach (amashaya), cecum (pakvashaya), rectum (uttaraguda), anus (adharaguda), small intestine (kshudrantra), large intestine (sthulantra), and omentum (vapavahana). [Cha.Sa. Sharira Sthana 7/10]

Embryology

Koshtha consists mainly of smooth organs like stomach and intestines that are inherited from mother. [Cha.Sa.Sharira Sthana 3/6] Tilburg et.al., analyzed 308 irritable bowel syndrome (IBS) patients along with 102 healthy controls and 36 inflammatory bowel disease patients of Caucasian traits for maternal inheritance of IBS. 17.5% of the participants had a probable maternal inheritance and the maternal polymorphism 16519T that is seen associated with multiple other functional disorders. This was significantly associated with the maternally inherited IBS.[3] As per Ayurvedic embryology, the precursor of gut is grossly seen in the fetus from the third month [Cha.Sa.Sharira Sthana 4/11] and attains full maturity by the seventh month. [Su.Sa.Sharira Sthana 3/30][2] The development of gut as per the western embryology starts from third week of intrauterine life and attains near-adult level functioning by 32 weeks.[4]

Physiology

Koshtha is the important site for digestion. All the three doshas and their subtypes play pivotal role in maintaining the physiology of koshtha. The prana vayu (a type of vata) propels the timely administered food to the koshtha. The bodhaka kapha (a type of kapha) in oral cavity senses the taste of food. The kledaka kapha moistens the food and subjects it to digestion. Further, pachaka pitta and samana vayu lead the role in division into essence (saara) and waste (kitta). Samana vayu is important in breaking down the moistened food into small particles for easy digestion by pachaka pitta. Further, the wastes of food are expelled by apana vayu. The essence is circulated by vyana vayu. Hence, the proper functioning of all three are necessary to maintain the equilibrium in the koshtha. In the transient stages of digestion (avasthapaka) the dosha are nourished in their respective abodes. Kapha, Pitta, and Vata in amashaya (upper gastrointestinal tract with stomach), pachyamanashaya (small intestine) and pakvashaya (large intestine) respectively. These parts of koshtha are primary seats of the corresponding dosha.

Grahani (lower part of stomach and duodenum) and agni (factors responsible for digestion and metabolism) are the most important structural and functional components of koshtha respectively. Grahani holds undigested food till the completion of digestion. It is the part of koshtha that forms the substratum for agni. The nature of grahani is crucial in deciding the nature of koshtha. When grahani is unable to retain the food till proper digestion or when agni is so weak that it is unable to facilitate proper digestion, the result is improperly formed metabolites or ama.

Types of koshtha

There are basically three types of koshtha:

1. Hard (krura), predominant with vata dosha and in vata prakriti individuals

2. Soft (mridu), predominant with pitta dosha and in pitta prakriti individuals

3. Medium or intermediate (madhya) predominant with kapha dosha and in kapha prakriti individuals. It is also seen in the individuals with equilibrium state of dosha in prakriti.

Assessment of koshtha

The dominant dosha plays key role in functions of koshtha. The absorption due to dryness (ruksha) property of vata dosha leads to hard bowel. The slow movement is bowel is due to heaviness (guru), steadiness (sthira), slowness (manda) properties of kapha dosha. The fast movement in bowel is due to stimulating (sara), sharply acting (tikshna) and fluid (drava) properties of pitta dosha. The dosha exert their influence over grahani. Obstruction and stagnation are observed in hard bowels (krura koshtha); whereas the fluidity is the dominating property in soft bowels (mridu koshtha). [Chakrapani commentary on Cha.Sa.Sutra Sthana 13/65-69]

The consistency of fecal matter is the primary tool for assessment of koshtha. In the context of oleation (snehana), the fecal consistency is parameter to assess oleation. In subjects who have been properly oleated, the feces are well-formed, evacuated in a smooth, unctuous, unobstructed manner and without stickiness. Whereas in insufficiently oleated subjects, fecal matter is dry and hard (pellet-like). In over-oleated cases, the fecal matter is poorly formed (resulting in sticky feces).[Cha.Sa.Sutra Sthana 13/57-59]

Pathways of diseases in koshtha

Koshtha is one of the disease pathways. It plays vital role in pathogenesis of following diseases: fever (jwara), diarrhea (atisara), vomiting (chhardi), sluggish bowel (alasaka), acute non-infectious gastroenteritis (visuchika), cough (kasa), bronchial asthma (shwasa), hiccups (hikka), abdominal distension (anaha), ascites (udara), splenomegaly (pleeha), internal variants of erysipelas (visarpa), edema (shotha), abdominal lumps (gulma), hemorrhoids (arsha), and abscesses (vidradhi). [Cha.Sa.Sutra Sthana 11/49] Certain diseases are observed more in specific types of koshtha. Udavarta (diseases due to improper or reverse movement of vata dosha) is a complication of hemorrhoids (arsha). In subjects with vata-predominant koshtha, the condition may develop without hemorrhoids (arsha). [A.Hr.Nidana Sthana 7/52][1]

Poor appetite (kshudha-mandya), indigestion (ajirna) and poor digested matter (ama) are the basic pathological entities related to the koshtha.

The first two stages among six stages of pathogenesis (shat-kriya kala) i.e. the accumulative stage (sanchaya) and the provocative stage (prakopa) are confined to koshtha. The former is characterized by accumulation of dosha in their sites and the latter by excess aggravation of dosha. In case of gut, the obstructed bowels leading to pain and abnormal movement of vata, acid reflux, thirst, burning sensation, aversion to food and heartburn can be observed in these stages. The third stage characterized by overflow and migration of doshas (prasara) shows signs indicating the involvement of koshtha like abdominal distension, burning sensation, anorexia, indigestion, and vomiting.[Su.Sa.Sutra Sthana 21/18-32][2]

Factors influencing gut

Gut is a highly dynamic system characterized by interaction with both intrinsic and extrinsic factors. Among the extrinsic factors, food, regimen, region, and season, and among the internal factors, the physical constitution, age, and psyche are the most crucial ones. All these factors directly or indirectly influence the digestion and metabolism (agni), both at the gut level and at the tissue level. All these effects culminate at the endpoint called ‘ojas’ or ‘bala’ that is the product of the total metabolic activities happening in living body.[Su.Sa.Sutra Sthana 15/19][2] The baseline nature of the gut is decided by the physical constitution of the individual. The grahani of a vata-dominant individual is also vata-dominant. Hence the digestive pattern becomes irregular. When the dominance is of pitta dosha, digestive pattern is strong or fast (tikshna). In case of dominance of kapha dosha, the digestive pattern is slow (manda). [Cha.Sa.Vimana Sthana 6/18] A study conducted to identify the gut microbe diversity among rural population of western India revealed signature microbes that showed prakriti-specific distribution patterns despite the dominance of Firmicutes and Bacteroidetes.[5]

Causes of impairment of agni and koshtha

Agni is impaired by inadequate food intake, indigestion, overeating, irregular eating habits, consumption of unhabituated, heavy, cold, dry, stale food, improper administration of bio-purificatory therapies, emaciation due to diseases, regional and climatic differences, suppression of urges. These are some of the primary causes of diminution of agni and the cascade of further adverse events in koshtha. [Cha.Sa.Chikitsa Sthana 15/41-44]

Even if the appropriate food has been ingested in appropriate amounts, if the subject is going through excessive stress, grief, fear, anger, improper diurnal cycle, then the digestion is prone to impairment. [Cha.Sa.Vimana Sthana 2/9] Gut interacts with brain via metabolic, endocrine, immune, and humoral mechanisms. Hence, gut health and mood, cognition and mental health operate in tandem.[6]

Therapeutic implications of koshtha

The objective of identification of koshtha are:

i. Diagnosis of the stage of disease (avastha)

ii. Decision of modality, drug, vehicle, and dosage

iii. Prognosis and assessment of therapeutic response

Diagnosis of stage of diseases

The stages of the diseases are based on multiple parameters. One of them is either the state of saama (associated with ama) or niraama (not associated with ama). Obstruction of channels, diminution of bala, heaviness, improper activity of vata, languor, indigestion, expectoration, difficulty in expelling waste matter, anorexia and tiredness are the cardinal features of saama state. The opposite features indicate niraama state.

Other important stages of diseases are subclinical or latent or dormant (lina dosha avastha) and clinical or manifested phase (vyakta dosha avastha). In former phase, the dosha stay dormant in the koshtha or in the circulatory channels. They manifest clinical features in favorable season, environment, region, etc. This leads to clinical phase. This stage is important to know, especially in allergy and other autoimmune pathologies, which exhibit seasonal flare-ups. [Su.Sa.Sutra Sthana 21/30][2], [A.Hr.Sutra Sthana 13/19][1]

The aggravated state when the dosha are ready to get expelled out (utklishta) is important state for purification therapies. The other state is when the dosha are not ready to get expelled out (anutklishta) state. This forms another dyad of disease stages. The former notes “vitiated and inclined to expulsion” and the latter its opposite.[Chakrapani commentary on Cha.Sa.Chikitsa Sthana 3/146] Mobile or unstable (chala) and stable (sthira) states also share similar meanings.

The primary objective of understanding koshtha is the administration of diet, medicines, and therapeutic procedures. [A.Hr.Sutra Sthana 18/15][1] In general, the guideline for quantity of food that is healthy for everyone has been recommended based on his or her appetite and the capacity of koshtha. The time for food intake is decided based on symptoms indicating digestion of previous meal. The ideal mealtime is when the bowel and bladder has been evacuated, the chest is clear, the doshas are optimum, the belching does not reflect any undigested food, sequentially followed by hunger, vata is in its normal direction, when the agni is well kindled, the senses are intact and open to perception, and lightness is perceived in the body. [A.Hr.Sutra Sthana 8/55][1]

In therapeutic purification procedures (panchakarma), the dosha are eliminated only when they are located or brought into koshtha. This is observed by the signs like fullness and distension of abdomen after oleation and sudation.[Cha.Sa.Sutra Sthana 15/11] Koshtha also plays a major role in deciding the dosage of medicines. Soft bowels (mridu koshtha) are easy to oleate and evacuate.[A.Hr.Sutra Sthana 18/35][1] These individuals usually attain the expected oleation by three days and purgated using mild laxatives like milk, jaggery, buttermilk, juices of sugarcane, grapes, and decoctions like that of Triphala (combination of Terminalia chebula, Terminalia bellirica and Phyllanthus emblica). The person with hard bowels takes about seven days to oleate and are also very difficult to purgate.[Cha.Sa.Sutra Sthana 13/65-69] This is the reason why mild forms of oleation mixed with food and drinks (vicharana) are indicated in soft bowel individuals. [Cha.Sa.Sutra Sthana 13/82] Medications like oils, marrow, etc. are advised in hard bowel individuals. Some other specific indications with respect to koshtha include that of oil in gut infested with worms (krimi koshtha), and muscle fats (vasa) in gut pains (koshtha ruja).

Sudation (swedana) is indicated mainly in hard bowel individuals (krura koshtha), especially in abdominal distension. It is not recommended in diseases arising due to pitta dosha with soft bowels (mridu koshtha). [Cha.Sa.Sutra Sthana 14/16,21] In koshtha, when vata afflicts the stomach (amashaya), initially dry sudation is to be done followed by unctuous sudation. When kapha dosha afflicts the large intestine (pakvashaya), the reverse order is to be followed. [Cha.Sa.Sutra Sthana 14/9]

Several pharmacological actions mentioned in Ayurveda revolve mainly around koshtha and its components. The actions that are specifically in relation with gut are: appetite stimulant (dipana), digestive stimulant (pachana), the digestion and propelling forward (anulomana), the action of expelling the adhered waste materials without digesting them (sramsana), doing the same function by liquifying (rechana), and by breaking the food items (bhedana).[Sha.Sa.Prathama Khanda/Chapter 4][7]

The Agni-koshtha bipolarity plays an important role in deciding medications and modalities. Some of them have been enlisted in the following table:

Table 1: Relation of agni and koshtha with diagnosis and management
Status of agni Status of koshtha Associated features Line of management
Strong (dipta) hard bowels (krura) Stiffness of upper and lower back, sacral region [Cha.Sa.Chikitsa Sthana 3/172] unctuous enema (anuvasana)
Strong (dipta) hard bowels (krura) Obstruction of flatus [Cha.Sa.Chikitsa Sthana 5/25] Nourishing foods and drinks that are unctuous and warm in properties
Strong (dipta) hard bowels (krura) Dryness, habituated to exercise, excess of Vata [A.Hr.Sutra Sthana 18/53-55][1] Therapeutic enema or pungent rectal suppositories followed by unctuous purgation
Weak (manda) mildly unctuous Abdominal pain, abdominal distension in abdominal lumps caused by vata (vatika gulma) [A.Hr.Chikitsa Sthana 14/29][1] Decoctions, powders, and tablets in medicated ghee
Weak (manda) mildly unctuous Abdominal pain, abdominal distension in abdominal lumps caused by kapha (kaphaja gulma) [Cha.Sa. Chikitsa Sthana 5/54] Decoctions, powders, and tablets
Weak (manda) mildly unctuous Kaphaja gulma, habituated to alcohol [Cha.Sa.Chikitsa Sthana 5/60] Medicated alcohol preparations (arishta)
Weak (manda) Heavy and sluggish bowels Kaphaja gulma, very mild pain, tendency to expel doshas, anorexia [Cha.Sa.Chikitsa Sthana 5/49] Therapeutic emesis (Vamana)
Weak (manda) hard bowels (krura) - Alkali (Kshara), salt (lavana) based preparations along with ghee followed by purgation [A.Hr. Sutra Sthana 18/52-53][1]

Current evidence and research on gut

Several domains of research have evolved around gut and its health. However, most of the research focus on microbial flora of gut. Ayurvedic literature mentions inherent microbes (sahaja krimi) that occupy the gut but are not detrimental to the host. [Chakrapani commentary on Cha.Sa.Vimana Sthana 7/9] Gut microbiota in health and disease is a zone of intense research. Gut flora is in constant interaction with the central nervous system, respiratory system, hepatobiliary system, cardiovascular system, skeletal system, and integumentary system probably via metabolites like butyrate and propionate.[8] Even in diseases that are apparently functional like functional gastrointestinal disorders and autism spectrum disorders, the role of gut microbiota has been identified.[9]

The gut flora patterns vary according to age, diet, and several other stimuli. The most conspicuous changes occur in the transmission from infancy to adulthood and from adulthood to senility. In infants (especially those who belong to developed societies), due to multiple reasons like formula feeds, caesarian births, improper antibiotic use leading to impaired gut flora composition, resulting in increased prevalence of allergic and autoimmune conditions among them. Supplementation with probiotics containing protective bacteria like Bifidobacterium longum it was found to show better colonization of gut microbes in breastfed infants at one year of age compared to infants without probiotic supplements.[10] Weaning is also a critical point in gut microbial diversification, wherein the pattern of gut microbiota changes from that of an infant to that of an adult.[11] Among old-age population, the gut flora pattern differentiates between healthy and non-healthy. Healthy ageing was characterized by decreasing variety of the core genera of microbes, especially bacteroides. The microbial variety also correlated with the survival rates of old adults.[12]

The interactions between gut flora and herbs are also emerging areas of research. It was observed that the microbiota metabolized the components of herbs to produce metabolites that significantly influence physiology. The herbs in turn modulated the composition of gut microbiota that in turn regulated their functioning.[13] The common Ayurvedic formulation Triphala was found to promote the growth of healthy bacteria, i.e., Bifidobacteria and Lactobacilli, and inhibit the growth of pathogenic bacteria like Escherichia coli. The active compounds in Triphala were metabolized by the gut microbiome to generate antioxidant compounds.[14] Ginger juice taken in a concentration 1.5 g/mL, for 7 days in a dose of 500 mg/kg/day increased the diversity of intestinal flora in young healthy individuals. Reduction was observed in Prevotella-to-Bacteroides ratio and pro-inflammatory microbes, and the juice also elevated the Firmicutes-to-Bacteroids ratio, Proteobacteria (anaerobic, antioxidant) and Faecalibacterium (anti-inflammatory).[15] Curcumin-supplemented diet was found to dose-dependently increase the survival rate and eradicate the tumor burden (at 0.5% concentration) in colitis-induced colon cancer models of IL-10 deficient mice. This action probably attributed to the increase in gut flora diversity and prevention of age-related dysbiosis.[16] Bio-purificatory procedures like bowel cleansing were also found to decrease the total intestinal microbial load by 31-fold and restore it within 14 to 28 days.[17] Rectal administration of buttermilk processed with Acorus calamus, Piper longum, Cyperus rotundus, Aegle marmelos, Anethum sowa, Randia spinosa, Trachyspermum ammi and Saussurea lappa for 15 days increased the abundances of Firmicutes, Proteobacteria and Deinococcus-Thermus in obese patients. Bacteroides abundance decreased, and the ratio of Firmicutes to Bacteroides increased from day 0 and 16 and then was back to baseline by day 45.[18]

Novel drug delivery mechanisms have also developed targeting the gut and related axes. There is emerging evidence related to skin-gut-brain axis which aims to harness the possibilities of transdermal route medicine administration to influence the gut status. Amla, Neem, Aloe and multiple other drugs have been previously studied in this respect.[19] Prebiotic, probiotic and symbiotic foods constitute a fast-growing industry having vast implications. Their interal administration during pregnancy, lactation, and postnatal life were found to influence the maternal and neonatal gut flora and hence improve maternal and neonatal outcomes.[20] Ayurvedic herbs have been evaluated in various studies for their prebiotic potential. Herbs like Glycyrrhiza glabra and Triphala have been identified to promote the growth of healthy bacteria and to reduce the pathogenic ones. They also influenced different groups of bacteria. Triphala increased the relative abundance of butyrate-producing bacteria whereas G. glabra increased that of propionate-producing bacteria.[21] Advances in rectal drug delivery like hollow, thermos-responsive, liquid, nanoparticle-based suppositories have opened new windows of opportunity, especially in subjects where oral, intravenous, and other drug routes are inaccessible.[22]

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References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Vagbhata. Ashtanga Hridayam. Edited by Harishastri Paradkar Vaidya. 1st ed. Varanasi: Krishnadas Academy;2000.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Sushruta. Sushruta Samhita. Edited by Jadavaji Trikamji Aacharya. 8th ed. Varanasi: Chaukhambha Orientalia;2005.
  3. ↑ van Tilburg MAL, Zaki EA, Venkatesan T, Boles RG. Irritable bowel syndrome may be associated with maternal inheritance and mitochondrial DNA control region sequence variants. Digestive Diseases and Sciences. 2014;59(7):1392–7.
  4. ↑ Bhatia A, Shatanof RA, Bordoni B. Embryology, Gastrointestinal. StatPearls [Internet]. 2021 May 8 [cited 2022 Apr 1]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK537172/
  5. ↑ Chauhan NS, Pandey R, Mondal AK, Gupta S, Verma MK, Jain S, et al. Western Indian Rural Gut Microbial Diversity in Extreme Prakriti Endo-Phenotypes Reveals Signature Microbes. Frontiers in Microbiology [Internet]. 2018;9:118. Available from: https://www.frontiersin.org/article/10.3389/fmicb.2018.00118
  6. ↑ Appleton J. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integrative Medicine: A Clinician’s Journal [Internet]. 2018 Aug 1 [cited 2022 Mar 19];17(4):28. Available from: /pmc/articles/PMC6469458/
  7. ↑ Sharangadhara. Sharangadhara Samhita. Translated from Sanskrit by K.R. Srikantha Murthy. Reprint ed. Varanasi: Chaukhambha orientalia;2016.
  8. ↑ Feng Q, Chen WD, Wang YD. Gut microbiota: An integral moderator in health and disease. Frontiers in Microbiology. 2018 Feb 21;9(FEB):151.
  9. ↑ de Palma G, Collins SM, Bercik P. The microbiota-gut-brain axis in functional gastrointestinal disorders. Gut Microbes. 2014;5(3).
  10. ↑ O’brien CE, Meier AK, Cernioglo K, Mitchell RD, Casaburi G, Frese SA, et al. Early probiotic supplementation with B. infantis in breastfed infants leads to persistent colonization at 1 year. [cited 2022 Mar 21]; Available from: https://doi.org/10.1038/s41390-020-01350-0
  11. ↑ Meng Q, Luo Z, Cao C, Sun S, Ma Q, Li Z, et al. Weaning Alters Intestinal Gene Expression Involved in Nutrient Metabolism by Shaping Gut Microbiota in Pigs. Frontiers in Microbiology. 2020 Apr 17;11:694.
  12. ↑ Wilmanski T, Diener C, Rappaport N, Patwardhan S, Wiedrick J, Lapidus J, et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nature Metabolism 2021 3:2 [Internet]. 2021 Feb 18 [cited 2022 Apr 5];3(2):274–86. Available from: https://www.nature.com/articles/s42255-021-00348-0
  13. ↑ An X, Bao Q, Di S, Zhao Y, Zhao S, Zhang H, et al. The interaction between the gut Microbiota and herbal medicines. Biomedicine & Pharmacotherapy. 2019 Oct 1;118:109252.
  14. ↑ Peterson CT, Denniston K, Chopra D. Therapeutic Uses of Triphala in Ayurvedic Medicine. Journal of Alternative and Complementary Medicine (New York, NY) [Internet]. 2017;23(8):607–14. Available from: files/1341/Peterson et al. - 2017 - Therapeutic Uses of Triphala in Ayurvedic Medicine.pdf
  15. ↑ Wang X, Zhang D, Jiang H, Zhang S, Pang X, Gao S, et al. Gut Microbiota Variation With Short-Term Intake of Ginger Juice on Human Health. Frontiers in Microbiology. 2021 Feb 23;11:2453.
  16. ↑ Mcfadden RMT, Larmonier CB, Shehab KW, Midura-Kiela M, Ramalingam R, Harrison CA, et al. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention. Inflamm Bowel Dis [Internet]. 2015 Jul 25 [cited 2022 Apr 1];21(11):2483. Available from: /pmc/articles/PMC4615313/
  17. ↑ Jalanka J, Salonen A, Salojärvi J, Ritari J, Immonen O, Marciani L, et al. Effects of bowel cleansing on the intestinal microbiota. Gut [Internet]. 2015 Oct 1 [cited 2022 Apr 6];64(10):1562–8. Available from: https://pubmed.ncbi.nlm.nih.gov/25527456/
  18. ↑ Mane S, Dixit KK, Lathwal N, Dhotre D, Kadus P, Shouche YS, et al. Rectal administration of buttermilk processed with medicinal plants alters gut microbiome in obese individuals. J Diabetes Metab Disord [Internet]. 2021 Dec 1 [cited 2022 Mar 19];20(2):1415–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/34900793
  19. ↑ Beri K. Perspective: Stabilizing the Microbiome Skin-Gut-Brain Axis with Natural Plant Botanical Ingredients in Cosmetics. Cosmetics [Internet]. 2018;5(2):37. Available from: http://www.mdpi.com/2079-9284/5/2/37
  20. ↑ Sohn K, Underwood MA. Prenatal and postnatal administration of prebiotics and probiotics. Seminars in Fetal and Neonatal Medicine [Internet]. 2017;22(5):284–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1744165X17300677
  21. ↑ Peterson CT, Sharma V, Uchitel S, Denniston K, Chopra D, Mills PJ, et al. Prebiotic Potential of Herbal Medicines Used in Digestive Health and Disease. J Altern Complement Med [Internet]. 2018 Jul 1 [cited 2022 Mar 19];24(7):656–65. Available from: https://pubmed.ncbi.nlm.nih.gov/29565634/
  22. ↑ Purohit TJ, Hanning SM, Wu Z. Advances in rectal drug delivery systems. Pharmaceutical Development and Technology [Internet]. 2018;23(10):942–52. Available from: https://www.tandfonline.com/doi/full/10.1080/10837450.2018.1484766
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