Keys to alopecia areata might lie in gut microbiome

SCOTTSDALE, ARIZ. – Wiping out the gut microbiome with antibiotics prevented alopecia areata in a study of mice, providing evidence that the gut microbiome may play a role in alopecia, Dr. James Chen reported at the annual meeting of the Society for Investigative Dermatology.

The finding shows that the bacterial culprits in alopecia “reside in the gut microbiome, and not in the skin,” said Dr. Chen, a postdoctoral research fellow in medical genetics at Columbia University, New York.

Alopecia areata is mediated by autoreactive NKG2D+ CD8+ T cells. Aberrations in the human microbiome underlie several other autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and type I diabetes, Dr. Chen noted. “The gut microbiome also has been linked to skin conditions, such as acne, psoriasis, and atopic dermatitis,” he added. “So we asked, if we deplete this microbiome with an antibiotic cocktail, do we see an effect on alopecia?”

To find out, he and his coinvestigators grafted skin from C3H/Hej mice, which spontaneously develop alopecia, onto healthy younger mice, causing them to develop alopecia 6-10 weeks later. “Strikingly, we found that treating unaffected mice with an oral antibiotic cocktail prior to grafting completely prevented the development of alopecia areata, and this remained true through 15 weeks,” he said. “This is the first evidence that the gut microbiome could be implicated in alopecia, based on the absence of the phenotype that we see in treated mice.”

The researchers also evaluated whether the skin microbiomes of antibiotic-treated and control mice differed, and determined that the skin samples resembled each other in terms of overall bacterial load and bacterial taxonomic clustering patterns. That suggests that the skin microbiome is not involved in alopecia areata, Dr. Chen said.

Finally, the investigators transferred NKG2D+ CD8+ T cells from the cutaneous lymph nodes of alopecic mice to normal mice that had been pretreated with antibiotics. The treated mice had little infiltration of these T cells into the skin, and lower overall T-cell levels than control mice, Dr. Chen reported.

The investigators are now testing combinations of antibiotics and fecal transplants to pinpoint which gut bacteria make mice susceptible to hair loss. Doing so “will have significant implications on both our understanding of alopecia areata susceptibility, as well as actionable therapeutic targets for treatment” in humans, Dr. Chen said.

The study was funded by the National Institutes of Health, the Medical Research Council, the Dermatology Foundation, Locks of Love Foundation, and NYSTEM (New York State Stem Cell Science). Dr. Chen had no financial disclosures.

SCOTTSDALE, ARIZ. – Wiping out the gut microbiome with antibiotics prevented alopecia areata in a study of mice, providing evidence that the gut microbiome may play a role in alopecia, Dr. James Chen reported at the annual meeting of the Society for Investigative Dermatology.

The finding shows that the bacterial culprits in alopecia “reside in the gut microbiome, and not in the skin,” said Dr. Chen, a postdoctoral research fellow in medical genetics at Columbia University, New York.

Alopecia areata is mediated by autoreactive NKG2D+ CD8+ T cells. Aberrations in the human microbiome underlie several other autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and type I diabetes, Dr. Chen noted. “The gut microbiome also has been linked to skin conditions, such as acne, psoriasis, and atopic dermatitis,” he added. “So we asked, if we deplete this microbiome with an antibiotic cocktail, do we see an effect on alopecia?”

To find out, he and his coinvestigators grafted skin from C3H/Hej mice, which spontaneously develop alopecia, onto healthy younger mice, causing them to develop alopecia 6-10 weeks later. “Strikingly, we found that treating unaffected mice with an oral antibiotic cocktail prior to grafting completely prevented the development of alopecia areata, and this remained true through 15 weeks,” he said. “This is the first evidence that the gut microbiome could be implicated in alopecia, based on the absence of the phenotype that we see in treated mice.”

The researchers also evaluated whether the skin microbiomes of antibiotic-treated and control mice differed, and determined that the skin samples resembled each other in terms of overall bacterial load and bacterial taxonomic clustering patterns. That suggests that the skin microbiome is not involved in alopecia areata, Dr. Chen said.

Finally, the investigators transferred NKG2D+ CD8+ T cells from the cutaneous lymph nodes of alopecic mice to normal mice that had been pretreated with antibiotics. The treated mice had little infiltration of these T cells into the skin, and lower overall T-cell levels than control mice, Dr. Chen reported.

The investigators are now testing combinations of antibiotics and fecal transplants to pinpoint which gut bacteria make mice susceptible to hair loss. Doing so “will have significant implications on both our understanding of alopecia areata susceptibility, as well as actionable therapeutic targets for treatment” in humans, Dr. Chen said.

The study was funded by the National Institutes of Health, the Medical Research Council, the Dermatology Foundation, Locks of Love Foundation, and NYSTEM (New York State Stem Cell Science). Dr. Chen had no financial disclosures.

SCOTTSDALE, ARIZ. – Wiping out the gut microbiome with antibiotics prevented alopecia areata in a study of mice, providing evidence that the gut microbiome may play a role in alopecia, Dr. James Chen reported at the annual meeting of the Society for Investigative Dermatology.

The finding shows that the bacterial culprits in alopecia “reside in the gut microbiome, and not in the skin,” said Dr. Chen, a postdoctoral research fellow in medical genetics at Columbia University, New York.

Alopecia areata is mediated by autoreactive NKG2D+ CD8+ T cells. Aberrations in the human microbiome underlie several other autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and type I diabetes, Dr. Chen noted. “The gut microbiome also has been linked to skin conditions, such as acne, psoriasis, and atopic dermatitis,” he added. “So we asked, if we deplete this microbiome with an antibiotic cocktail, do we see an effect on alopecia?”

To find out, he and his coinvestigators grafted skin from C3H/Hej mice, which spontaneously develop alopecia, onto healthy younger mice, causing them to develop alopecia 6-10 weeks later. “Strikingly, we found that treating unaffected mice with an oral antibiotic cocktail prior to grafting completely prevented the development of alopecia areata, and this remained true through 15 weeks,” he said. “This is the first evidence that the gut microbiome could be implicated in alopecia, based on the absence of the phenotype that we see in treated mice.”

The researchers also evaluated whether the skin microbiomes of antibiotic-treated and control mice differed, and determined that the skin samples resembled each other in terms of overall bacterial load and bacterial taxonomic clustering patterns. That suggests that the skin microbiome is not involved in alopecia areata, Dr. Chen said.

Finally, the investigators transferred NKG2D+ CD8+ T cells from the cutaneous lymph nodes of alopecic mice to normal mice that had been pretreated with antibiotics. The treated mice had little infiltration of these T cells into the skin, and lower overall T-cell levels than control mice, Dr. Chen reported.

The investigators are now testing combinations of antibiotics and fecal transplants to pinpoint which gut bacteria make mice susceptible to hair loss. Doing so “will have significant implications on both our understanding of alopecia areata susceptibility, as well as actionable therapeutic targets for treatment” in humans, Dr. Chen said.

The study was funded by the National Institutes of Health, the Medical Research Council, the Dermatology Foundation, Locks of Love Foundation, and NYSTEM (New York State Stem Cell Science). Dr. Chen had no financial disclosures.