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7. Microbes, Their Metabolites, and Effector Molecules: A Pharmacological Perspective for Host-Microbiota Interaction

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2019 | OriginalPaper | Book chapter

Abstract

The human microbiota and probiotics are key players to modulate human health. Microbial cells, as a whole, have either been known to physically react with intestinal surfaces or to produce some enzymes and metabolites to impart a positive or negative impact on human health. Moreover, their specialized metabolites have a profound role in the generation of multivariate clinical responses in humans, with an influence on hosts ’metabolism and immunity. Gut microbiota and probiotics are known for their influence on hosts ’physiology.
We review clinical trials based on microbiota composition to correlate health status of humans with their gut microbiota, along with few examples of effects of microbial perturbation on health and disease. The chapter also explains the roles of metabolites of human microbiota, in addition to their impacts on hosts ’physiology. Besides the positive influences of microbes on humans, negative effects of the microbial metabolism, such as inactivating the pharmacological activity of drugs are also discussed, Selected examples for the roles of gut microbiota in human metabolism, using their enzymatic repertoire for degradation of otherwise indigestible dietary components are reviewed. We present the mode of action of newly identified effector molecules, polysaccharides, outer membrane proteins, pili, muropeptides, and CpG-rich DNA, both for human microbiota and probiotics (Lactobacillus and Bifidobacterium strains). Besides effector molecules, clinical outcomes of probiotics (as whole live cells) are also discussed. Moreover, health-improving probiotic metabolites, including vitamins, bacteriocins, and bioactive peptides, are reviewed. In the end, a new perspective of developing a microbial global positioning system (mGPS) for segregation of human population on the basis of their microbiota is discussed.

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literature
Go back to reference Aggarwal S, Upadhyay A, Shah D, Teotia N, Agarwal A, Jaiswal V (2014) Lactobacillus GG for treatment of acute childhood diarrhea: an open labeled, randomized controlled trial. Indian J Med Res 139 (3): 379-385 Aggarwal S, Upadhyay A, Shah D, Teotia N, Agarwal A, Jaiswal V (2014) Lactobacillus GG for treatment of acute childhood diarrhea: an open labeled, randomized controlled trial. Indian J Med Res 139 (3): 379-385
Go back to reference Agustina R, Bovee-Oudenhoven IM, Lukito W, Fahmida U, van de Rest O, Zimmermann MB, Firmansyah A, Wulanti R, Albers R, van den Heuvel EG, Kok FJ (2013) Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years. J Nutr 143 (7): 1184-1193. https: // doi. org / 10. 3945 / jn. 112.166397 CrossRef Agustina R, Bovee-Oudenhoven IM, Lukito W, Fahmida U, van de Rest O, Zimmermann MB, Firmansyah A, Wulanti R, Albers R, van den Heuvel EG, Kok FJ (2013) Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years. J Nutr 143 (7): 1184-1193. https: // doi. org / 10. 3945 / jn. 112.166397 CrossRef
Go back to reference Arboleya S, Martinez-Camblor P, Solís G, Suárez M, Fernández N, de los Reyes-Gavilán CG, Gueimonde M (2017) Intestinal microbiota and weight-gain in preterm neonates. Front Microbiol 8: 183. https: // doi. org / 10. 3389 / fmicb. 2017. 00183 CrossRef Arboleya S, Martinez-Camblor P, Solís G, Suárez M, Fernández N, de los Reyes-Gavilán CG, Gueimonde M (2017) Intestinal microbiota and weight-gain in preterm neonates. Front Microbiol 8: 183. https: // doi. org / 10. 3389 / fmicb. 2017. 00183CrossRef
Go back to reference Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, Subbarao P (2015) Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med 7 (307): 307ra152. https: // doi. org / 10. 1126 / scitranslmed. aab2271 CrossRef Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM , Lefebvre DL, Subbarao P (2015) Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med 7 (307): 307ra152. https: // doi. org / 10. 1126 / scitranslmed. aab2271CrossRef
Go back to reference Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M (2011) Enterotypes of the human gut microbiome. Nature 473: 174-180. https: // doi. org / 10. 1038 / nature09944 CrossRef Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M (2011) Enterotypes of the human gut microbiome. Nature 473: 174-180. https: // doi. org / 10. 1038 / nature09944CrossRef
Go back to reference Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331 (6015): 337-341. https: // doi. org / 10. 1126 / science. 1198469 CrossRef Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331 (6015): 337-341. https: // doi. org / 10. 1126 / science. 1198469CrossRef
Go back to reference Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S (2013) T reg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500: 232-236. https: // doi. org / 10. 1038 / nature12331 CrossRef Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S (2013) T reg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500: 232-236. https: // doi. org / 10. 1038 / nature12331CrossRef
Go back to reference Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101 (44): 1507-1519. https: // doi. org / 10. 1017 / S000711451300387 5 CrossRef Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101 (44): 1507-1519. https: // doi. org / 10. 1017 / S000711451300387 5CrossRef
Go back to reference Balmer ML, Schürch CM, Saito Y, Geuking MB, Li H, Cuenca M, Kovtonyuk LV, McCoy KD, Hapfelmeier S, Ochsenbein AF, Manz MG (2014) Microbiota-derived compounds drive steady-state granulopoiesis via MyD88 / TICAM signaling. J Immunol 193 (10): 5273-5283. https: // doi. org / 10. 4049 / jimmunol. 1400762 CrossRef Balmer ML, Schürch CM, Saito Y, Geuking MB, Li H, Cuenca M, Kovtonyuk LV, McCoy KD, Hapfelmeier S, Ochsenbein AF, Manz MG (2014) Microbiota-derived compounds drive steady-state granulopoiesis via MyD88 / TICAM signaling. J Immunol 193 (10): 5273-5283. https: // doi. org / 10. 4049 / jimmunol. 1400762 CrossRef
Go back to reference Booijink CC, El Aidy S, Rajilić Stojanović M, Heilig HG, Troost FJ, Smidt H, Kleerebezem M, De Vos WM, Zoetendal EG (2010) High temporal and inter individual variation detected in the human ileal microbiota. Environ Microbiol 12 (12): 3213-3227. https: // doi. org / 10. 1111 / j. 1462-2920. 2010. 02294. x CrossRef Booijink CC, El Aidy S, Rajilić Stojanović M, Heilig HG, Troost FJ, Smidt H, Kleerebezem M, De Vos WM, Zoetendal EG (2010) High temporal and inter individual variation detected in the human ileal microbiota. Environ Microbiol 12 (12): 3213-3227. https: // doi. org / 10. 1111 / j. 1462-2920. 2010. 02294. xCrossRef
Go back to reference Caminero A, Galipeau HJ, McCarville JL, Johnston CW, Bernier SP, Russell AK, Jury J, Herran AR, Casqueiro J, Tye-Din JA, Surette MG (2016) Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology 151 (4): 670-683. https: // doi. org / 10. 1053 / j. gastro. 2016. 06. 041 CrossRef Caminero A, Galipeau HJ, McCarville JL, Johnston CW, Bernier SP, Russell AK, jury J, Herran AR, Casqueiro J, Tye-Din JA, Surette MG (2016) Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology 151 (4): 670-683. https: // doi. org / 10. 1053 / j. gastro. 2016. 06.041CrossRef
Go back to reference Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R, Calignano A (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 17 (12): 1519-1528. https: // doi. org / 10. 3748 / wjg. v17. i12. 1519 CrossRef Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R, Calignano A (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 17 (12): 1519-1528. https: // doi. org / 10. 3748 / wjg. v17. i12. 1519 CrossRef
Go back to reference Chang HY, Chen JH, Chang JH, Lin HC, Lin CY, Peng CC (2017) Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: an updated meta-analysis. PLoS One 12 (2): e0171579. https: // doi. org / 10. 1371 / journal. pone. 0171579 CrossRef Chang HY, Chen JH, Chang JH, Lin HC, Lin CY, Peng CC (2017) Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: an updated meta-analysis. PLoS One 12 (2): e0171579. https: // doi. org / 10. 1371 / journal. pone. 0171579CrossRef
Go back to reference Claes IJ, Lebeer S, Shen C, Verhoeven TL, Dilissen E, De Hertogh G, Bullens DM, Ceuppens JL, Van Assche G, Vermeire S, Rutgeerts P (2010) Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clin Exp Immunol 162 (2): 306-314. https: // doi. org / 10. 1111 / j. 1365-2249. 2010. 04228. x CrossRef Claes IJ, Lebeer S, Shen C, Verhoeven TL, Dilissen E, De Hertogh G, Bullens DM, Ceuppens JL, Van Assche G, Vermeire S, Rutgeerts P (2010) Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clin Exp Immunol 162 (2): 306-314. https: // doi. org / 10. 1111 / j. 1365-2249. 2010. 04228. xCrossRef
Go back to reference Claes IJ, Segers ME, Verhoeven TL, Dusselier M, Sels BF, De Keersmaecker SC, Vanderleyden J, Lebeer S (2012) Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG. Microb Cell Factories 11 (1): 161. https: // doi. org / 10. 1186 / 1475-2859-11-161 CrossRef Claes IJ, Segers ME, Verhoeven TL, Dusselier M, Sels BF, De Keersmaecker SC, Vanderleyden J, Lebeer S ( 2012) Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG. Microb Cell Factories 11 (1): 161. https: // doi. org / 10. 1186 / 1475-2859-11-161CrossRef
Go back to reference Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN (2010) Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16 (2): 228-231. https: // doi. org / 10. 1038 / nm. 2087 CrossRef Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN (2010) Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16 (2): 228-231. https: // doi. org / 10. 1038 / nm. 2087 CrossRef
Go back to reference Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM (2014) Exercise and associated dietary extremes impact on good microbial diversity. Well. https: // doi. org / 10. 1136 / gutjnl-2013-306541 CrossRef Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M , Jeffery IB, Wood-Martin R, Kerins DM (2014) Exercise and associated dietary extremes impact on gut microbial diversity. Well. https: // doi. org / 10. 1136 / gutjnl-2013-306541CrossRef
Go back to reference Corr SC, Li Y, Riedel CU, O’Toole PW, Hill C, Gahan CG (2007) Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A 104 (18): 7617-7621. https: // doi. org / 10. 1073 / pnas. 0700440104 CrossRef Corr SC, Li Y, Riedel CU, O'Toole PW, Hill C, Gahan CG (2007) Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A 104 (18): 7617-7621. https: // doi. org / 10. 1073 / pnas.0700440104CrossRef
Go back to reference Costa DJ, Marteau P, Amouyal M, Poulsen LK, Hamelmann E, Cazaubiel M, Housez B, Leuillet S, Stavnsbjerg M, Molimard P, Courau S (2014) Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN study). Eur J Clin Nutr 68 (5): 602-607. https: // doi. org / 10. 1038 / ejcn. 2014. 13 CrossRef Costa DJ, Marteau P, Amouyal M, Poulsen LK, Hamelmann E, Cazaubiel M, Housez B, Leuillet S, Stavnsbjerg M, Molimard P, Courau S (2014) Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN study). Eur J Clin Nutr 68 (5): 602-607. https: // doi. org / 10. 1038 / ejcn. 2014. 13 CrossRef
Go back to reference Culpepper T, Christman MC, Nieves C Jr, Specht GJ, Rowe CC, Spaiser SJ, Ford AL, Dahl WJ, Girard SA, Langkamp-Henken B (2016) Bifidobacterium bifidum R0071 decreases stress-associated diarrhea-related symptoms and self-reported stress: a secondary analysis of a randomized trial. Benefic Microbes 7 (3): 327-336. https: // doi. org / 10. 3920 / BM2015.0156 CrossRef Culpepper T, Christman MC, Nieves C Jr, Specht GJ, Rowe CC, Spaiser SJ, Ford AL, Dahl WJ, Girard SA, Langkamp-Henken B (2016) Bifidobacterium bifidum R0071 decreases stress-associated diarrhea-related symptoms and self-reported stress: a secondary analysis of a randomized trial. Benefic Microbes 7 (3): 327-336. https: // doi. org / 10. 3920 / BM2015. 0156CrossRef
Go back to reference Dahiya DK, Renuka, Puniya M, Shandilya UK, Dhewa T, Kumar N, Kumar S, Puniya AK, Shukla P (2017) Gut microbiota modulation and its relationship with obesity using prebiotic fibers and probiotics: a review.Front Microbiol 8: 563. https: // doi. org / 10. 3389 / fmicb. 2017. 00563 CrossRef Dahiya DK, Renuka, Puniya M, Shandilya UK, Dhewa T, Kumar N, Kumar S, Puniya AK, Shukla P (2017) Gut microbiota modulation and its relationship with obesity using prebiotic fibers and probiotics: a review. Front Microbiol 8: 563. https: // doi. org / 10. 3389 / fmicb. 2017. 00563CrossRef
Go back to reference Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, Duong CP, Flament C, Lepage P, Roberti MP, Routy B (2016) Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45 (4): 931-943. https: // doi. org / 10. 1016 / j. immuni. 2016. 09.009 CrossRef Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V , Duong CP, Flament C, Lepage P, Roberti MP, Routy B (2016) Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45 (4): 931-943. https: // doi. org / 10. 1016 / j. immuni. 2016. 09.009CrossRef
Go back to reference de Angelis M, Bottacini F, Fosso B, Kelleher P, Calasso M, Di Cagno R, Ventura M, Picardi E, van Sinderen D, Gobbetti M (2014) Lactobacillus rossiae, a vitamin B12 producer, represents a metabolically versatile species within the genus Lactobacillus. PLoS One 9 (9): e107232. https: // doi. org / 10. 1371 / journal. pone. 0107232 CrossRef de Angelis M, Bottacini F, Fosso B, Kelleher P, Calasso M, Di Cagno R, Ventura M, Picardi E. , van Sinderen D, Gobbetti M (2014) Lactobacillus rossiae, a vitamin B12 producer, represents a metabolically versatile species within the genus Lactobacillus. PLoS One 9 (9): e107232. https: // doi. org / 10. 1371 / journal. pone. 0107232 CrossRef
Go back to reference De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156 (1): 84-96. https: // doi. org / 10. 1016 / j. cell. 2013. 12. 016 CrossRef De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156 (1): 84-96. https: // doi. org / 10. 1016 / j. cell. 2013. 12. 016 CrossRef
Go back to reference the best G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, Müller M, Groen AK, Hooiveld GJ, Bakker BM, Reijngoud DJ (2013) Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol 305 (12): 900-910. https: // doi. org / 10. 1152 / ajpgi. 00265. 2013 CrossRef den Beste G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, Müller M, Groen AK, Hooiveld GJ, Bakker BM, Reijngoud DJ (2013) Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol 305 (12): 900-910. https: // doi. org / 10. 1152 / ajpgi. 00265. 2013 CrossRef
Go back to reference Dennis-Wall JC, Culpepper T, Nieves C, Rowe CC, Burns AM, Rusch CT, Federico A, Ukhanova M, Waugh S, Mai V, Christman MC (2017) Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial. Am J Clin Nutr 105 (3): 758-767. https: // doi. org / 10. 3945 / ajcn.116.140012 CrossRef Dennis-Wall JC, Culpepper T, Nieves C, Rowe CC, Burns AM, Rusch CT, Federico A, Ukhanova M , Waugh S, May V, Christman MC (2017) Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind , placebo-controlled, randomized trial. Am J Clin Nutr 105 (3): 758-767. https: // doi. org / 10. 3945 / ajcn.116.140012CrossRef
Go back to reference Depeint F, Tzortzis G, Vulevic J, I'Anson K, Gibson GR (2008) Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind , crossover, placebo-controlled intervention study. Am J Clin Nutr 87 (3): 785-791. https: // doi. org / 10. 1093 / ajcn / 87. 3. 785 CrossRef Depeint F, Tzortzis G, Vulevic J, I'Anson K, Gibson GR (2008) Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind, crossover, placebo-controlled intervention study. Am J Clin Nutr 87 (3): 785-791. https: // doi. org / 10. 1093 / ajcn / 87. 3. 785 CrossRef
Go back to reference Deptula P, Kylli P, Chamlagain B, Holm L, Kostiainen R, Piironen V, Savijoki K, Varmanen P (2015) BluB / CobT2 fusion enzyme activity reveals mechanisms responsible for production of active form of vitamin B12 by Propionibacterium freudenreichii. Microb Cell Factories 14: 186. https: // doi. org / 10. 1186 / s12934-015-0363-9 CrossRef Deptula P, Kylli P, Chamlagain B, Holm L, Kostiainen R, Piironen V, Savijoki K, Varmanen P (2015 ) BluB / CobT2 fusion enzyme activity reveals mechanisms responsible for production of active form of vitamin B12 by Propionibacterium freudenreichii. Microb Cell Factories 14: 186. https: // doi. org / 10. 1186 / s12934-015-0363-9CrossRef
Go back to reference Deptula P, Chamlagain B, Edelmann M, Sangsuwan P, Nyman TA, Savijoki K, Piironen V, Varmanen P (2017) Food-like growth conditions support production of active vitamin B12 by Propionibacterium freudenreichii 2067 without DMBI, the lower ligand base, or cobalt supplementation. Front Microbiol 8: 368. https: // doi. org / 10. 3389 / fmicb. 2017. 00368 CrossRef Deptula P, Chamlagain B, Edelmann M, Sangsuwan P, Nyman TA, Savijoki K, Piironen V, Varmanen P (2017 ) Food-like growth conditions support production of active vitamin B12 by Propionibacterium freudenreichii 2067 without DMBI, the lower ligand base, or cobalt supplementation. Front Microbiol 8: 368.