Kyle’s mom looks so good after her fecal transplant that everyone wants to get their hands on her goods. Cartman and the boys jump into the quest for the best microbiome.
The episode starts with Sheila speaking to the women of South Park about how the women should be treated the same as the men. Halfway through her speech, however, she has a diarrhoea attack and starts vomiting everywhere. Mrs. Testaburger leads her out.
At Hell's Pass Hospital, the doctor speaks to Kyle and Ike about their mom's illness, explaining that she has a bacterial infection, and she will be treated with a fecal transplant. Kyle and Ike are disgusted, and make a pact not to tell anyone. Unfortunately, as soon as Sheila gets out of hospital, she tells all her friends about her procedure.
At Café Monet, Sheila tells Linda, Laura and Harriet about how great she feels after her fecal transplant. Harriet asks if she can have some of Sheila's poo for a DIY fecal transplant, since the doctor refused to do it. Sheila refuses, saying that Harriet shouldn't do it if the doctor said no. When she steps away, Harriet and the other moms insult her, with Harriet calling her a cunt.
Kyle watches a DVD about fecal transplants. He learns that bacteria is everywhere, and that half of his body is microorganisms. Kyle then tells the other boys about microorganisms, but they don't care. Harriet comes over to them and asks Kyle to get some of Sheila's poo in exchange for Jedi Fallen Order. Kyle refuses, and the boys fail to persuade him to do it.
The boys subsequently break into Kyle's house and mess with the pipes in order to get Sheila's poo when she goes to the toilet. Kyle finds them, but they still manage to get the poo.
Kyle goes to the doctor to talk about the microorganisms, and about people swapping microbiomes. He asks if people are going to start getting microbiomes from athletic people, like Tom Brady. The doctor realises Tom Brady's poo is the cure (or the "spice melange"). Meanwhile, Mr. Mackey speaks to the boys about the stolen faeces. He asks him to do it again, but with Tom Brady's poo instead.
On Main Street, Linda and Laura meet Harriet, who has lost weight thanks to the DIY fecal transplant. Sheila finds her and questions where she got the faeces from, but Harriet refuses to tell, and leaves. The three moms insult her behind her back, with Laura telling Sheila what Harriet called her.
Later at the cafe, the three moms eat when Harriet bursts in angrily, explaining that she got sick thanks to Sheila's poo. Linda and Laura then reveal that they stole some of the leftover poo to do fecal transplants, and the three start vomiting and pooing all over the cafe.
The boys manage to convince Tom Brady's agent to let them stay at his house by saying that Kenny is dying. With everyone looking to get some of Tom Brady's poo, other people are already waiting for Tom Brady. When he enters, one of them lets slip that they want poo, and Tom tries to kick them all out. Microorganisms take over Kyle's body, who bursts in before the boys can be kicked out. He notices the bookcase that he's been seeing in his dreams, and reveals a hidden room behind it. In the room, there are multiple jars with poo in, enough to cure everyone.
At Hells Pass, the doctor explains to Harrison Yates that half of South Park has the bacterial disease. He explains this is due to the moms using a turkey baster for DIY fecal transplants, since the turkey basters haven't been used for a year and therefore are teeming with bacteria. The boys arrive with Tom Brady's poo and the doctor uses it to treat all the patients. The moms then apologise to each other and become friends again.