wow...let's break this down
"A 5.56 AR will overpenetrate more than handguns or shotguns"
.223 Drywall Penetration: Results
click on the above link and read the test. While it is ammunition dependent, a 5.56/.223 can have excellent terminal effects AND limit overpenetration. A 5.56 is much more capable of doing damage to a person and quickly stopping a threat than a handgun and MUCH more capable than a .22LR...view the below...
AR-15 Tribute - YouTube
45ACP Speer 200gr +P Gold Dot impacting ballistic gelatin (slow motion) - YouTube
22LR CCI 40gr Velocitor PLHP impacting ballistic gelatin (42,000 frames/sec)! - YouTube
The faster/lighter .223/5.56 projectiles(especially ballistic tipped) break up pretty readily when going through walls and quickly shed energy. Handgun/shotgun projectiles aren't going fast enough to break apart and largely truck through MANY walls in a relatively straight line, with enough momentum on the other side to still adequately penetrate a person. In fact, most current handgun defensive loadings are made specifically so they will penetrate the fbi minimum 12" w/ expansion AFTER going through a wall.
Summary....WIN 5.56 in an AR
"Use birdshot for defense in a shotgun"
watch this....
Friends don't let Friends shoot Birdshot for HD - YouTube
and this...
Shotshell comparison Slow Motion - YouTube
...realize that 4-6" of penetration makes one nasty, but shallow wound. Most structures that cause a person to physiologically stop being a threat(bone structure, CNS, high-flow vasculature), are pretty deep towards the back of your thoracic cavity. In the case of the CNS, most of it is behind a large amount of bone structure. Your projectile has to make it through clothes, skin, adipose tissue, muscle, fluid, and then bone to reach really anything important(keep in mind most of your thoracic cavity is shielded by your rib-cage).
You're going to want a projectile that can penetrate somewhere close to 12" to get to that important stuff. In the case of a shotgun, it's going to be a #4 buckshot load or larger. I personally favor #1 buck as the best load for defense for a 12ga.
".22 is useless for defense"
Well no...it's been killing people for a long time now and can be quite effective. If it's between a .22 and fighting at close range with a handheld cutting or striking weapon, the .22 wins. Especially in a rifle, .22 can create a good bit of trauma and when combined with good shot placement, it can kill.
The issue is that compared to other cartridges, it creates MUCH less trauma. When you've got a .22 load just over 100 ftlb's of energy to do work compared to a 9/40/45 with around 400 ftlbs...it's easy to see the centerfire loads have the ability to create much more damage. bump up to .223 with 1,200 ftlbs or so and it's no contest which one is mo'betta. That extra energy is used to crush/tear/displace tissue that the .22 wont. It means you're going to do more damage and potentially stop the threat faster with similar shot placement.
In defense speed & shot placement is the name of the game. with similar shot placement, it will take a person much longer to stop being a threat with a .22 wound. It will likely also require many more shots sent their way to do enough damage to stop them. if I jump into hypothetical world right quick, a .223 may stop a threat with 2 hits on center mass. Before they can get to you, a .22 may require 10+ hits. Assume you're getting a pretty good rate of 15% shots on target...you're sending many more shots into the walls behind the threat with the .22 than you are with the much more effective .223. ....but a .22 still can stop a threat, it's just not as good as a centerfire loading for handguns or carbines.
People that would use .22's are ones that physically cannot handle larger calibers. Some senior citizens or people with grip-strength issues may be best served by a m&p22 pistol, because the slide is easy to manipulate and the recoil is extremely easy to control. If you're able to handle a more powerful cartridge, you should.